共查询到20条相似文献,搜索用时 7 毫秒
1.
B L Doughty E A Ottesen T E Nash S M Phillips 《Journal of immunology (Baltimore, Md. : 1950)》1984,133(2):993-997
An in vitro model of granuloma formation was used to study the cellular immune responses of Schistosoma mansoni-infected patients. The purposes of this study were to determine the relationship of granulomatous hypersensitivity to S. mansoni eggs in recent, well-defined infections and long-term chronic infections, and to determine the role of T cell subsets (OKT3, 4, and 8) defined by monoclonal antibodies in granulomatous hypersensitivity. Peripheral blood mononuclear cells obtained from patients with recent S. mansoni infections demonstrated increased granulomatous hypersensitivity responses in vitro when compared to peripheral blood mononuclear cells obtained from patients infected for 5 yr or more. The selective removal of infected for 5 yr or more. The selective removal of OKT3+ or OKT4+ cells reduced the ability of peripheral blood mononuclear cells to form granulomas in vitro. Positive selection for OKT4+ T cells produced optimal granulomatous hypersensitivity when compared to that produced by the unfractionated peripheral blood mononuclear cell population. OKT8+ cells demonstrated no ability to form granulomas in vitro. Selective removal of OKT8+ T cells produced variable results in the ability of the remaining peripheral blood mononuclear cells to form granulomas in vitro. These studies demonstrate the feasibility of investigating granulomatous hypersensitivity and immunoregulatory mechanisms operative in S. mansoni-infected patients by using in vitro technology. 相似文献
2.
Effector activity of OKT4+ and OKT8+ T-cell subsets in lectin-dependent cell-mediated cytotoxicity against adherent HEp-2 cells 总被引:4,自引:0,他引:4
The role of OKT4+ and OKT8+ T-cell subsets was studied in lectin-dependent cell-mediated cytotoxicity (LDCC) against adherent HEp-2 human epipharynx carcinoma target cells. LDCC was evaluated by detachment from the monolayer of [3H]thymidine prelabeled HEp-2 cells in a 24-hr assay with a concanavalin A (Con A) dose of 25 microgram/ml at effector:target cell ratios of 5:1, 25:1, and 50:1. Under these conditions but without Con A considerable natural cell-mediated cytotoxicity (NCMC) was not elicited; however, the cytotoxicity was significantly augmented in the presence of Con A (=LDCC) by sheep erythrocyte rosette-forming T lymphocytes and by both OKT4+ and OKT8+ T-cell fractions. LDCC activity by isolated OKT8+ T cells was superior to that by OKT4+ T cells and unfractionated T lymphocytes. By contrast, addition of either OKT4+ or OKT8+ T cells together with unfractionated T lymphocytes, or OKT4+ and OKT8+ T cells mixed at ratios of 1:1, 1:2, and 2:1, to target cells did not result in major differences in comparison of LDCC activities by these mixed effector cell populations with each other or with that by unfractionated T lymphocytes. Parallel studies were carried out to determine the effect of OKT4+ and OKT8+ T-cell subsets on the Con A-induced proliferation of peripheral blood mononuclear cells (PBMC). While OKT8+ T cells inhibited the mitogenic response to Con A, OKT4+ T lymphocytes had no major effect. A higher responsiveness of the OKT8+ to OKT4+ T-cell subset in LDCC to HEp-2 targets and in Con A-induced lymphocyte proliferation is suggested. 相似文献
3.
Defective suppressor cell function mediated by T8+ cell lines from patients with progressive multiple sclerosis 总被引:5,自引:0,他引:5
J Antel M Bania A Noronha S Neely 《Journal of immunology (Baltimore, Md. : 1950)》1986,137(11):3436-3439
Activated suppressor cell function, induced with either concanavalin A or OKT3 and mediated by either unfractionated mononuclear cells or "panning" enriched T8+ cells, freshly isolated from peripheral blood, is reduced in patients with progressive multiple sclerosis (MS) as compared with control donors. In this study, we generated T8+ cell lines from the peripheral blood of these same patients and controls. Suppressor activity, mediated by T8+ cells exposed to OKT3 on days 1, 7, and 14 of culture and then treated with mitomycin C on day 16, was significantly reduced in the MS group (mean percent suppression 13% +/- 5) as compared with the control group (68% +/- 6, n = 8, p less than 0.001). No differences were noted in [3H]thymidine uptake by the OKT3-stimulated T8+ cell lines of MS and control groups. Mean percent suppression mediated by T4+ cell lines did not differ between MS and control groups (15% +/- 4, n = 3, vs 22% +/- 2, n = 4). These current data suggest that the previously observed defect in T8+ cell-mediated activated suppressor cell function in MS is a persistent one, favoring the postulate that the defect reflects intrinsic alterations in this cell population rather than a transient effect of serum factors on T8+ cell function. 相似文献
4.
Cellular origin and interactions involved in gamma-interferon production induced by OKt3 monoclonal antibody 总被引:16,自引:0,他引:16
T W Chang D Testa P C Kung L Perry H J Dreskin G Goldstein 《Journal of immunology (Baltimore, Md. : 1950)》1982,128(2):585-589
OKT3 monoclonal antibody, a human T cell mitogen, induced interferon production by cultured mononuclear cells at 10(-11) M concentrations. Interferon was secreted only under conditions wherein OKT3 was mitogenic, and production was correlated with cell proliferation. Thus, like mitogenesis, interferon secretion reached a peak 3 days after OKT3 stimulation, was inhibited by a factor(s) in human serum, and required 1000 times higher concentrations of Fab and F(ab')2 fragments of OKT3 for induction. The interferon was most likely of "gamma" (immune) type, because pH 2 and 56 degrees C treatments denatured it, whereas anti-alpha or -beta interferon antibodies did not. Mononuclear cells were fractionated into subpopulations that contained OKT4+ cells (helper/inducer T cells), OKT8+ cells (cytotoxic/suppressor T cells), and OKM1+ cells (monocytes) by combining sheep red blood cell rosetting and complement-mediated lysis using monoclonal antibodies against specific cell types. Both OKT4+ and OKT8+ cells proliferated upon OKT3 stimulation with the absolute requirement of OKM1+ cells. However, OKT4+ cells plus OKM1+ cells were necessary for the secretion of interferon. Studies with selective pretreatments with mitomycin C suggested that gamma-interferon was secreted by the OKT4+ cells and that the OKM1+ population subserved an accessory function. 相似文献
5.
Functional properties of T cells in patients with chronic T gamma lymphocytosis and chronic T cell neoplasia 总被引:6,自引:0,他引:6
H C Rümke F Miedema I J ten Berge F Terpstra H J van der Reijden R J van de Griend H G de Bruin A E von dem Borne J W Smit W P Zeijlemaker C J Melief 《Journal of immunology (Baltimore, Md. : 1950)》1982,129(1):419-426
The expanded T cell populations of 10 patients with either T gamma lymphocytosis (five patients) or proven chronic T cell malignancy (five patients) were analyzed with respect to functional activity in vitro, including proliferative responses to mitogens, cytotoxic activity (killer [K] and natural killer [NK] cell activity), and regulatory activity on pokeweed mitogen- (PWM) induced immunoglobulin (Ig) synthesis (help and suppression) in comparison with marker phenotypes. In each of the five patients with T gamma lymphocytosis, only one out of three functionally distinct cell types was found: T gamma-K cells, T gamma-S cells, or T gamma-NK/K cells, which mediated K-cell activity, suppressive activity, and both NK and K cell activity, respectively. An expanded T gamma-K cell population was demonstrated in three patients with neutropenia with or without recurrent infections. T gamma-S cells were found in a patient with severe hypogammaglobulinemia, and T gamma-NK/K cells in one patient with asymptomatic lymphocytosis. T gamma-K and T gamma-S cells had a similar surface-marker profile (E+ or E-, Fc gamma+, OKT1-3+4-8+I1-M1-), whereas that of T gamma-NK/K cells was different (E+, Fc gamma+, OKT1-3-4-8-I1+M1+). Longitudinal studies of three untreated patients with T gamma-K lymphocytosis showed that the abnormalities were persistent but not progressive. In contrast, five patients with chronic T cell malignancy (two with T-CLL, two with cutaneous T cell lymphoma [CTCL], and one with T-PLL) all had progressive disease. The neoplastic cells in these cases were E+, Fc gamma-OKT1+4+6- with variable expression of the OKT3 and OKT8 markers. The only functional activity observed in these cells was suppressive activity by OKT3-4+8- cells from a patient with CTCL. 相似文献
6.
Nonspecific suppressor T cells cause decreased mixed lymphocyte culture reactivity in bone marrow transplant patients 总被引:2,自引:0,他引:2
M Harada M Ueda S Nakao K Kondo K Odaka S Shiobara K Matsue T Mori T Matsuda 《Journal of immunology (Baltimore, Md. : 1950)》1986,137(2):428-432
Decreased reactivity in mixed lymphocyte culture (MLC) was observed in patients within 1 yr after allogeneic and autologous bone marrow transplantation. Suppressor activity of peripheral blood mononuclear cells (PBMC) from transplant patients was studied by adding these cells as modulator cells to a bidirectional MLC with cells from normal individuals. PBMC from transplant patients markedly suppressed MLC reactivity in a dose-dependent manner. Suppressor activity was present in cells forming rosettes with sheep erythrocytes. Treatment of modulator cells with monoclonal antibodies against T cell differentiation antigens (OKT8, OKIa1) and complement completely abolished suppression of MLC. Suppressor activity was unaffected by 30 Gy irradiation. Suppressor activity declined gradually after transplantation and was inversely correlated with MLC reactivity of each patient at a significant level (p less than 0.01). These observations suggest that OKT8+ Ia+ radioresistant suppressor T cells play a role in the development of decreased MLC reactivity observed during the early post-transplant period. 相似文献
7.
G S Haas E Halperin D Doseretz R Linggood P S Russell R Colvin L Barrett A B Cosimi 《Journal of immunology (Baltimore, Md. : 1950)》1984,132(2):1026-1030
To better understand the immunologic effects of lymphoid irradiation (LI), blood levels of T cell subsets were sequentially monitored in 15 patients before, during, and after irradiation treatment for Hodgkin's disease. Blood levels of all lymphocytes, T cells, and T cell subsets (defined by OKT4 and OKT8) fell dramatically and in similar proportions during early therapy, reaching levels less than 20 to 25% of control by the completion of mantle irradiation, and continuing at very depressed levels through the completion of therapy. Blood levels of OKT8-reactive (OKT8+) cells returned to pretreatment levels (402 +/- 38/mm3 vs 360 +/- 32/mm3 pretreatment) between 6 to 8 mo after LI, whereas blood levels of OKT4-reactive (OKT4+) cells returned to only 42% of previous values (242 +/- 22/mm3 vs 584 +/- 34/mm3 pretreatment) over the same period. The pre-LI ratio of OKT4+ to OKT8+ cells was 1.85 +/- 0.24 and fell to 0.65 +/- 0.05 between 6 to 8 mo after LI. During the recovery period, discrepancies of 208 +/- 32 cells/mm3 (3 to 5 months post LI) and 198 +/- 32 cells/mm3 (6 to 8 mo post LI) developed between the blood levels of OKT3+ cells and the sum of OKT4+ and OKT8+ cells. This suggests the emergence of OKT4+/OKT3-, OKT8+/OKT3-, and/or OKT4+/OKT8+ cells. In five patients, the sum of OKT4+ and OKT8+ cells was compared with the number of cells simultaneously co-stained by OKT4 and OKT8. It appeared that a significant proportion of the cells were OKT4+/OKT3- and OKT8+/OKT3- lymphocytes. We concluded that LI is similarly cytotoxic to peripheral blood T cell subpopulations. The reversed ratio after LI is a result of a slower repopulation of the peripheral blood by OKT4+ cells relative to OKT8+ cells. T cells after LI show a high degree of antigenic immaturity. It is postulated that the bone marrow that lies outside the fields of treatment and contains predominantly immature OKT8+/OKT3- cells is a major source of T cells repopulating the peripheral blood after LI. 相似文献
8.
T Sakane H Kotani S Takada Y Murakawa Y Ueda 《Journal of immunology (Baltimore, Md. : 1950)》1983,131(2):753-761
The autologous mixed lymphocyte reaction (MLR) is thought to be part of a regulatory role of T cells on B cell function. OKT4+, but not OKT8+, cells can proliferate in response to autologous non-T cells. Moreover, the OKT4+ cell population activated early in the course of autologous MLR functioned as inducer cells for the differentiation of B cells, whereas later in the response, the activated OKT4+ cells were particularly enriched in suppressor cells. A part of the autologous MLR appears to be an important pathway for the activation of feedback suppression mechanisms among cells contained within the OKT4+ populations. Patients with systemic lupus erythematosus (SLE) were studied with regard to the following OKT4+ cell functions in vitro after activation in the autologous MLR: a) proliferative response, and b) helper and suppressor activities for differentiation of B cells. A marked reduction in the proliferative response of OKT4+ cells was observed in SLE patients. SLE OKT4+ cells activated in the autologous MLR could function as helper cells but could not exert any suppressor activity. This OKT4+ cell abnormality was present regardless of the disease activity, and occurred in the absence of autoantibodies including anti-T cell antibodies. Instead, SLE anti-T cell antibodies could preferentially eliminate cells bearing the OKT8+ phenotype characteristic of suppressor cells in populations of normal T cells. These results suggest that the defect in the suppressor circuits among OKT4+ cell populations is intrinsic to SLE lymphocytes and that the OKT8+ suppressor T cell defect is caused by antibodies produced by the B cells of SLE patients. 相似文献
9.
Glucocorticoid receptors in subpopulations of human lymphocytes defined by monoclonal antibodies 总被引:1,自引:0,他引:1
Glucocorticoid receptors (GR) were investigated in subpopulations of lymphocytes identified by monoclonal antibodies. Purified T (OKT3+) and non-T lymphocyte subpopulations were isolated from human peripheral blood using Degalan bead columns coated with rabbit anti-human IgG. Purified subpopulations of OKT4+ and OKT8+ lymphocytes were obtained by coating the nonadherent population (T cells) from the first column with OKT4+ or OKT8+ and pouring it into a second Degalan column, coated with goat anti-mouse IgG. GR content and affinity were analyzed by a whole cell assay with [3H]dexamethasone as tracer. The numbers of GR in lymphocyte subpopulations (OKT3+ cells, non-T cells, OKT4+, and OKT8+ cells) were nearly equal. It is concluded that the differential effects of glucocorticoids on the circulatory kinetics of OKT4+ and OKT8+ cells probably are not related to differences in glucocorticoid receptors of these T-cell subpopulations. 相似文献
10.
Delineation of suppressor and helper activity within the OKT4-defined T lymphocyte subset in human newborns 总被引:6,自引:0,他引:6
Lymphocytes taken from the cord blood of newborns have active suppressor activity. Using in vitro PWM-stimulated cocultures, unfractionated T cells from newborns potently suppressed the expected immunoglobulin G (IgG) synthesis of their mothers' peripheral blood lymphocytes (PBL). Using positive and negative selection techniques, we characterized the active suppressor cell as expressing the OKT4+T8- phenotype. This cord blood lymphocyte subset suppressed maternal IgG synthesis after depletion of maternal suppressor cells, implicating the ability of newborn T cells to suppress directly rather than by inducing adult suppressor activity. Sublethal amounts (1500 rad) of gamma-irradiation fully abrogated the suppressor activity of cord blood T lymphocytes. Radioresistant cord T cells provided T cell help. Irradiation of cord OKT4+ and OKT8+ populations and their subsequent culture with maternal B cells determined that helper activity was a radioresistant subpopulation of the OKT4+ subset. These results indicate significant differences in the functional properties of T cell subsets from adults and newborns. Population studies determined that cord blood lymphocytes had a greater proportion of OKT4+ cells and lower proportion of OKT8+ cells than PBL from unrelated adults. The mothers tested had similar proportions of OKT4+ cells as their babies, and these levels are significantly higher than those of unrelated adults. 相似文献
11.
L M Wahl I M Katona R L Wilder C C Winter B Haraoui I Scher S M Wahl 《Cellular immunology》1984,85(2):373-383
Rapid separation of large numbers of human peripheral blood mononuclear cells into fractions enriched for B lymphocytes, T lymphocytes, or monocytes was accomplished by counterflow centrifugal elutriation (CCE). The first fraction contained 98% of the platelets. Ten additional fractions containing subpopulations of mononuclear cells were collected by sequential increases in the flow rate while maintaining a constant centrifuge speed. Analysis of the fractions using monoclonal antibodies revealed that fraction 2, which was free of esterase-positive monocytes, was highly enriched for B cells. T lymphocytes (OKT3+) were the predominant cell type found in fraction 4. No enrichment for T-lymphocyte-helper (OKT4+) or -suppressor (OKT8+) subpopulations was observed in the lymphocyte containing fractions. Three fractions (7-9), highly enriched for esterase-positive cells, were predominantly OKM1+ monocytes with no evidence of selective separation of monocyte subpopulations. Thus, cell fractions enriched for B cells, T cells, and monocytes could be obtained, by utilizing CCE, in large enough quantities to enable analysis of their functional properties. Of particular interest was the ability to separate small, resting B lymphocytes from monocytes. 相似文献
12.
J P Antel M B Bania A Reder N Cashman 《Journal of immunology (Baltimore, Md. : 1950)》1986,137(1):137-141
Concanavalin A (Con A)-induced suppressor activity has previously been shown to be reduced in multiple sclerosis (MS) patients with active clinical disease. In this study, we demonstrate that OKT3, as well as Con A induced suppressor activity mediated by unfractionated peripheral blood mononuclear cells is reduced in patients with the progressive form of MS. By performing reconstitution experiments involving E+, T4+, or T8+ cells derived from either MS patients or controls, and normal allogeneic macrophages or E- cells, we sought to define the cellular basis for this suppressor defect. In both MS and control groups, E+ cells were required to obtain measurable levels of suppression. Suppressor levels induced by Con A-activated cultures containing E+ cells from MS patients were lower than those induced by those containing control donor E+ cells. Suppression mediated by T8+ cells from MS patients was also lower than for controls. In the control group, suppression mediated by T8+ cells exceeded that mediated by T4+ cells; such differences were not apparent in the MS group. These results suggest that although Con A-induced suppression can be mediated by a number of T and non-T cell subsets, the functional suppressor defect measured in the MS population does involve the T8+ cell subset. 相似文献
13.
D Geissler L Lu E Bruno H H Yang H E Broxmeyer R Hoffman 《Journal of immunology (Baltimore, Md. : 1950)》1986,137(8):2508-2513
Cellular and humoral influences of T lymphocytes on human megakaryocyte colony formation in vitro were assessed by using a microagar system. Megakaryocyte colony formation from nonadherent low density T lymphocyte-depleted (NALDT-) bone marrow cells was increased significantly after the addition of aplastic anemia serum (AAS) or purified megakaryocyte colony-stimulating factor (Meg-CSF). The addition of conditioned medium obtained from phytohemagglutinin-stimulated T lymphocytes replaced, at least partially, the requirement for AAS or purified Meg-CSF for the growth of megakaryocyte colonies. The cellular influence of T lymphocytes and T lymphocyte subsets on megakaryocyte colony formation was assessed by removing either T cells from nonadherent peripheral blood mononuclear cells with monoclonal OKT4, OKT8, or OKT3 antibodies plus complement, or by adding back populations of bone marrow or blood T4+ or T8+ lymphocytes, isolated by means of fluorescence-activated cell sorting, respectively, to NALDT--bone marrow or -blood cells. When sorted T cell subpopulations were added to a fixed number of NALDT--bone marrow or -peripheral blood cells in the presence of AAS or Meg-CSF, T4+ cells enhanced megakaryocyte colony formation and T8+ cells decreased it. These studies demonstrate that although the stimulation of megakaryocytic progenitor cells by Meg-CSF may not require the presence of monocytes or T lymphocytes, T4+ lymphocytes enhance and T8+ lymphocytes down-regulate megakaryocyte colony formation induced by Meg-CSF. These observations suggest that the immune system is capable of modulating the proliferative response of human megakaryocytic progenitor cells to Meg-CSF. 相似文献
14.
J A O'Malley A Nussbaum-Blumenson D Sheedy B J Grossmayer H Ozer 《Journal of immunology (Baltimore, Md. : 1950)》1982,128(6):2522-2526
Positive and negative selection procedures combined with cytofluorographic analysis and lysis with monoclonal antibodies were utilized to identify the T lymphocyte subset that produces human gamma interferon (gamma-IFN) (formerly referred to as "immune" or "type II" interferon) in response to mitogen stimulation. Lymphocytes were separated on the basis of their Fc receptors for IgG or IgM, their nonreactivity with IgM or IgG antibodies, and their reactivity with the monoclonal antibodies OKT4, OKT8, OKT11a, and OKM1. Isolated T cell subsets were incubated with the gamma-IFN inducer, phytohemagglutinin. Three days after induction, the cell supernatants were harvested and assayed for interferon. The T cell subset that produces gamma-IFN was identified as E rosette positive with the phenotype: T gamma, T non-micro, OKM1+, OKT4-, OKT8- and OKT11a+. gamma-IFN production by cells was resistant to doses of x-irradiation that abrogate mitogen-induced T suppressor function but was highly sensitive to low doses of 4-hydroperoxycyclophosphamide. These data demonstrate that gamma-IFN is produced by the T gamma, OKM1+ lymphocyte subset, but these cells may also require the presence of accessory monocytes for elaboration of gamma-IFN. The anti-proliferative activity of gamma-IFN may be responsible for the previously described suppressor function of this subset, and gamma-IFN production by T gamma cells may distinguish this subset from the suppressor/cytotoxic functions of the OKT8+ subset or the mitogen-induced OKT4+ suppressor. 相似文献
15.
Four patients with peripheral neuropathy and nonmalignant monoclonal gammopathy with anti-myelin-associated glycoprotein (MAG) antibodies were studied to determine whether secretion of anti-MAG IgM antibodies by B cells was autonomous, or whether the monoclonal B cells were responsive to T cells. Secretion of anti-MAG IgM by isolated B cells was stimulated by the addition of increasing numbers of pokeweed mitogen (PWM)-activated autologous OKT4+ helper T cells in all four patients. Secretion of anti-MAG IgM by peripheral blood lymphocytes was dependent on the ratio of OKT4+ T helper cells to OKT8+ T suppressor/cytotoxic cells. In three patients with an OKT4+ to OKT8+ T-cell ratio of 2:1, PWM activation stimulated secretion of anti-MAG IgM; in one patient with an OKT4+ to OKT8+ ratio of 1:2, activation by PWM suppressed anti-MAG IgM secretion. These studies suggest that the monoclonal B cells that secrete anti-MAG IgM are responsive to regulatory T cells. 相似文献
16.
Functional analysis of human T cell subsets defined by monoclonal antibodies. III. Regulation of helper factor production by T cell subsets 总被引:8,自引:0,他引:8
Y Thomas J Sosman L Rogozinski O Irigoyen P C Kung G Goldstein L Chess 《Journal of immunology (Baltimore, Md. : 1950)》1981,126(5):1948-1951
In the present report we extended our previous studies demonstrating that obligatory T-T interactions are important in regulating human immune responses in vitro. Functionally distinct human T cell subsets were isolated by complement-mediated lysis using the monoclonal antibodies OKT4 and OKT8. Evidence was obtained that during allogeneic interactions, OKT4+, but not OKT8+, responder T cells are required to generate helper factor(s) capable of polyclonally activating human B cells independent of additional T cell help. Importantly, the alloantigen-induced helper factor(s) production and/or release was found to be suppressed by addition of graded numbers of radiosensitive OKT8+ cells. On the other hand, no evidence was obtained that supernatant derived from alloactivated OKT8+ cells could counterbalance the helper activity generated in the presence of supernatant from alloactivated OKT4+ cells. Furthermore, OKT8+ cells, known to suppress PWM-driven B cell differentiation in the presence of OKT4+ cells, do not suppress B cell differentiation induced by preformed helper factor even in the presence of OKT4+ cells. These data further underscore the importance of functional T-T interactions in immunoregulation in vitro and support the idea that the target of suppression of B cell differentiation, induced either by alloantigen-triggered helper factor or PWM, are OKT4+ cells and not B cells themselves. 相似文献
17.
Lymphocyte subpopulations in the neonate: identification of an immature subset of OKT8-positive, OKT3-negative cells 总被引:7,自引:0,他引:7
R Maccario L Nespoli G Mingrat A Vitiello A G Ugazio G R Burgio 《Journal of immunology (Baltimore, Md. : 1950)》1983,130(3):1129-1131
T cell subpopulations of lymphocytes from cord blood (CBL) of 24 newborns and from peripheral blood (a-PBL) of 24 healthy adult volunteers were assessed in T cell-enriched, T cell depleted and unseparated lymphocyte fractions by using OKT3, 4, 6, and 8 monoclonal antibodies. The results show that T cell-enriched CBL include adult numbers of OKT3+, OKT4+, OKT6+ and OKT8+ lymphocytes whereas the T cell-depleted fraction consists of a high percentage of OKT8+, OKT3-, non-E rosette-forming cells bearing a PNA receptor. The presence of the PNA receptor and the lack of the OKT3+ antigen strongly support the hypothesis that the subset of OKT8+ cells in cord blood includes immature T lymphocytes that may represent an intermediate stage between thymocytes and mature peripheral T cells. 相似文献
18.
Concanavalin A triggers T lymphocytes by directly interacting with their receptors for activation 总被引:9,自引:0,他引:9
R Palacios 《Journal of immunology (Baltimore, Md. : 1950)》1982,128(1):337-342
Anti-HLA-DR antibodies did not inhibit concanavalin A-(Con A) induced T cell proliferation or the generation of suppressor cells capable of inhibiting immunoglobulin synthesis in autologous mononuclear cells after pokeweed mitogen stimulation. Nylon-wool purified T cells (pretreated with anti-HLA-DR antibody and C) exposed to Con A acquired responsiveness to interleukin 2 (IL 2) and were able to absorb this growth factor, whereas nonlectin-treated cells did not respond to IL 2 and could not absorb it. In the presence of interleukin 1 (IL 1), Con A stimulated the synthesis of IL 2 in purified OKT4+ lymphocytes but not OKT8+ cells. However, in the absence of IL 1, neither resting OKT4+ nor Con A-treated OKT4+ cells produced IL 2. Con A by itself did not directly stimulate macrophages to synthesize IL 1, although it could do so in the presence of OKT4+ but not OKT8+ lymphocytes. In addition, Con A induced proliferation of purified T cells provided IL 1 was supplied to the cultures. Cyclosporin A rendered Con A-treated T cells unresponsive to IL 2, made lectin-stimulated OKT4+ lymphocytes unable to respond to IL 1, and inhibited the synthesis of IL 2. Furthermore, this drug abrogated the Con A-stimulated synthesis of IL 1 by acting on OKT4+ lymphocytes and not on macrophages. Finally, cyclosporin-A suppressed the proliferative response and the generation of suppressor T cells induced by Con A. The following are concluded: 1) HLA-DR antigens do not seem to play any role in the triggering of T cells by Con A, and macrophages participate in lectin-induced activation of T cells mainly by providing IL 1. 2) Cyclosporin-A inhibits activation of T cells by interfering with the mechanism by which Con A stimulates T lymphocytes. 3) Con A triggers T lymphocytes by directly interacting with their receptors for activation. 相似文献
19.
Peter M. Anderson Fritz H. Bach Augusto C. Ochoa 《Cancer immunology, immunotherapy : CII》1988,27(1):82-88
Summary A wide variety of human cancers currently have no effective treatment and are potential targets for lymphokine-activated killer (LAK) cellular immunotherapy. Relapsed acute lymphocytic leukemia (ALL) and neuroblastoma are two of the major therapeutic challenges in pediatric oncology today. However, one problem which makes LAK immunotherapy in children particularly difficult is obtaining the large numbers of cells required. Present adult therapeutic LAK protocols have utilized short-term (5 day) cultures of interleukin-2 (IL2)-activated cells which are initially obtained from leukophersis. Since routine use of this procedure in small children is not practical, we have investigated a different approach to obtain increased cell numbers by activation of peripheral blood mononuclear cells with OKT3, a mitogenic anti-CD3 monoclonal antibody, and IL2. Cell growth and LAK activity in OKT3+IL2-activated cultures were compared to cultures activated with IL2 alone in 2 children with relapsed ALL and 2 children with stage IV neuroblastoma. OKT3+IL2-activated cultures had marked increases in cell number: after 14 days the OKT3+IL2-activated cultures yielded an approximately 500-fold increase in cell number compared to a 7-fold increase for cultures activated with IL2 alone. In vitro 51Cr release assays were used to estimate LAK activity of the cultures at 7 and 14 days. When tested against HL60, a natural killer (NK)-resistant tumor cell line, not only were total cytolytic units greatly increased in OKT3+IL2-stimulated cultures but lytic activity on a per cell basis (lytic units/1×106 cells) had also markedly increased on day 14 of culture. Phenotypic analysis demonstrated that 80% to 90% of cells in OKT3+IL2-stimulated cultures were CD3+ T cells. Variable low percentages of CD16+ NK cells were seen in these cultures. In summary, OKT3+IL2 activation resulted in a large increase in cell yield and the development of high level LAK activity using peripheral blood mononuclear cells from children with cancer. This approach may facilitate the utilization of increased cell numbers in future adoptive immunotherapy protocols, especially in pediatric patients.Supported by the Children's Cancer Research Fund, and the USPHS Training Grant T32CA09445Supported by NIH AI17687, AI18326, AI19007, and AI72626 相似文献
20.
Characterization of the natural killer-like lymphocytes in rheumatoid synovial fluid 总被引:4,自引:0,他引:4
IgG Fc- cytotoxic cells found in the synovial fluid of patients with rheumatoid arthritis have natural killer (NK)-like characteristics but can kill NK-resistant cell lines as well. The phenotype of these cells was defined by complement-mediated lysis with monoclonal antibodies. The synovial fluid killer cell activity was significantly reduced by treatment with complement and OKT11 and 4F2, but the cytotoxic T cells did not express the NK-related antigens OKM1 and Leu-7, nor the cytotoxic T lymphocyte-specific antigen, OKT8. These results demonstrate that the synovial fluid killer cells resemble the activated T cells generated in an autologous mixed leukocyte reaction or in the treatment of peripheral blood mononuclear cells with interleukin 2, and they are distinct from the conventional NK cells found in blood. 相似文献