The adjuvant activity of synthetic N-acetylmuramyl-dipeptide: evidence of initial target cells for the adjuvant activity.

MurNAc-l-Ala-d-isoGln (N-acetylmuramyl-l-alanyl-d-isoglutamine, MDP), a synthetic compound, acts as an adjuvant on the humoral immune response and on the T cell-mediated immune response. In this report, we attempted to directly demonstrate the initial target cells of MDP for its adjuvant activity in vitro by using cell separation procedures.It was demonstrated that MDP enhanced the immune response following direct interaction with antigen-stimulated T and B lymphocytes, but nonstimulated lymphocytes, shortly after triggering by antigen, and that there was no macrophage requirement for MDP to elicite the adjuvant action in the primary anti-SRBC PFC response in vitro. It has also been demonstrated that the adjuvant activity of MDP is due to an enhancing effect which is different from the possible mitogenic activity to spleen cells and MDP replaces neither a function of macrophages, which is substituted by 2-mercaptoethanol nor a helper function of T cells.     

Maintenance of hyporesponsiveness to antigen by a distinct subclass of T lymphocytes.

Immunization with increasing doses of SRBC, in excess of 10(8), results in a progressive decline in the anti-SRBC PFC response. This hyporesponsive state is antigen specific and is reflected in a decrease of both T helper and B antibody-forming activity. We asked whether the apparent defect of T helper activity reflected a) an absence of alphaSRBC helper T cell activity, or b) the presence of SRBC-specific suppressor T cells within the hyporesponsive population. Our results indicate that at least a portion of hyporesponsiveness noted after antigen exposure to large doses of antigen can be ascribed to specific suppressor T cell activation. Fractionation of the suppressive T cell population using Ly antiserum showed that specific suppressive activity was mediated by a subclass of T cells (Ly2+), distinct from that committed to express helper function (Ly1).     

Difference in genesis between antigen-induced IgM antibody-forming cells and B-cell mitogen-induced IgM antibody-forming cells in mouse spleen cell cultures.

To determine the mechanisms in the triggering of thymus-independent lymphocytes (B cells) for development into antibody-forming cells (AFC), genesis of IgM AFC elicited polyclonally by nonspecific stimulation with B-cell mitogen, such as nystatin and bacterial lipopolysaccharide, was compared with that of IgM AFC specifically elicited by antigenic stimulation, using mouse spleen cell cultures as an experimental system and sheep erythrocytes (SRBC) as a test antigen. Considering that differentiation and proliferation are necessary cellular events for precursor B cells to develop into AFC, the effect of different antimetabolic agents on the generation of each type of AFC in spleen cell cultures was examined. The generation of anti-SRBC IgM hemolysin plaque-forming cells (PFC) in B-cell mitogen-stimulated spleen cell cultures was found to be less susceptible to X-irradiation or mitomycin C than that in the SRBC-stimulated cultures. These apparently paradoxical results were affiirmed using colcemid as an inhibitor of cell mitosis and hydroxyurea (HU) as an inhibitor of cellular DNA synthesis. Thus, when spleen cell cultures responding to either SRBC or B-cell mitogen were exposed to colcemid or HU during a period from 2 days to 3 days after the stimulation, the exponential generation of anti-SRBC IgM PFC in the cultures responding to SRBC was completely halted, whereas that in the cultures responding to B-cell mitogen was not. Furthermore, N⁶, O^2′ -dibutyryl adenosine 3′, 5′ -cyclic monophosphoric acid was found to halt the exponential generation of antigen-induced anti-SRBC IgM PFC but not that of the B-cell mitogen-induced anti-SRBC IgM PFC. From these results it was suggested that B-cell mitogen might stimulate precursor Bμ cells at a late stage in the differentiative pathway to develop into AFC without cell division, and that antigenic stimulation might stimulate relatively primitive precursor Bμ cells to proliferate and then differentiate into AFC. Based on this idea, mechanisms in the triggering of B-cell activation are discussed.     

Immunological properties of Fc receptor on lymphocytes. 2. Differentiation from FcR- to FcR+ cells and their functional differences in in vitro antibody response.

In in vitro plaque-forming cell (PFC) response to particulate as well as to soluble antigen, the functional difference between Fc receptor-bearing (FcR⁺) and nonbearing (FcR^?) murine splenic lymphocytes was analyzed using the EA rosetting method. In the secondary anti-horse red blood cell (HRBC) response of C3H mice, FcR^? cells showed higher IgM and IgG responses than did FcR⁺ cells. When nylon wool (NW)-purified T cells primed with keyhole limpet hemocyanin (KLH) were fractionated into FcR^? and FcR⁺ T cells, helper activity was proven in the former subset in the cooperation with syngeneic spleen cells primed with dinitrophenylated ascaris extract (DNP-Asc). FcR⁺ T cells showed essentially no helper activity. When FcR^? cells were cultured, neogenesis of FcR⁺ cells was observed on Days 3 to 5. The conversion from FcR^? to FcR⁺ cells was prominent in B cells (40 to 50%), whereas NW-purified nonadherent FcR^? T cells converted poorly (15 to 20%). The converting process was accelerated slightly by mitogens, but was least affected by antigens. To examine the possible contribution of neogeneic FcR⁺ T cells in the helper activity, KLH-primed FcR^? T cells were precultured for 7 days with homologous antigen. The specific helper activity of the cultured T cells proved to be unaffected by the depletion of neogeneic FcR⁺ T cells by EA rosetting. The neogeneic FcR⁺ T cells had no helper activity. It was thus suggested that helper T cells remain in the FcR^? cell fraction and do not convert to the FcR⁺ state during the cooperating process.     

Cloned T cells with "co-helper" activity. I. Biologic activities of the clone

Clones of sheep erythrocyte-(SRBC) specific helper T cells with the surface phenotype Thy-1+, Ly-1+, Ly-2- have been derived that grow in vitro in the absence of exogenous antigen or added growth factors. The IL 2-independent clone, 101.6 has been shown to produce a supernatant factor that augments the primary anti-SRBC but not anti-burro RBC responses of whole spleen cells or Ly-1 T plus B cell cultures. The supernatant does not help B cells directly. This augmenting activity is terminated "co-helper" because the enhancement requires the presence of normal Ly-1 T cells. The supernatant of 101.6 was not shown to contain IL 2; co-helper activity was distinguishable from IL 2 activity by absorption with SRBC but not with Con A blasts, and we observed that co-helper activity does not act on spleen cells that differ at the major histocompatibility complex.     

Suppression of in vitro antibody responses by Listeria primed spleen cells.

Spleen cells from mice primed with virulent Listeria monocytogenes do not develop an anti-SRBC plaque forming cell response to SRBC in culture. Furthermore, when Listeria primed spleen cells are co-cultured with normal spleen cells and SRBC, the anti-SRBC response of the normal cells is suppressed. Listeria primed spleen cells from T cell depleted donors are equally effective at immunosuppression. The immunosuppressive effect does not appear to be due to the presence of the bacterium or its products per se in the cultures. Furthermore, the effect cannot be transferred across a 0.45 μm pore membrane. Kinetic studies show that the immunosuppressive effect develops by 2 days post-Listeria inoculation and peaks by Day 6. Low doses of Listeria are not immunosuppressive and produce some enhancement effect. From these results, it is suggested that a population of non-T cell dependent cells develop in Listeria primed hosts that nonspecifically suppress the response of B cells to an unrelated antigen in culture.     

Antigen-initiated B lymphocyte differentiation. V. Electrophoretic separation of different subpopulations of AFC progenitors for unprimed IgM and memory IgG responses to the NIP determinant.

Spleen cells from CBA mice were separated by continuous, free-buffer film cell electrophoresis, and the capacity of cells in different fractions to mount an adoptive immune response specific for the NIP hapten determined. Experimental conditions were such that AFC progenitor B cells were measured, rather than helper or suppressor T cells. The IgM response of unprimed animals (a virgin or antigen inexperienced population) and the IgG response of long-term hapten-primed animals (a B memory cell population) were compared. The results indicated physical and biological heterogeneity in splenic B cells, with AFC progenitors for unprimed IgM and memory IgG responses being extensively separated.AFC progenitors for a primary IgM response in normal, germ-free and athymic mouse spleen, and bone marrow, separated into three distinct populations. Two of these were of much higher mobility than the typical splenic B cells and separated in the T cell zone. These cells produced a relatively early peak response of AFC after stimulation.AFC progenitors for a secondary IgG response were predominantly typical low-mobility B cells. Three regions of activity were separated, one overlapping part of the IgM progenitors. The slowest migrating activity peaks corresponded to the mobility of some recirculating B cells. These cells produced a more delayed AFC response after stimulation.AFC from the spleens of immunised mice separated as a single, broad, mediummobility peak distinct from most B cells and AFC progenitors. IgM and IgG (memory) AFC had similar electrophoretic characteristics.     

Mechanism of Epstein-Barr virus-induced human B-lymphocyte activation

The mechanism of Epstein-Barr virus (EBV) activation of human B lymphocytes toward Ig synthesis was investigated in a direct anti-sheep red blood cell (SRBC) antibody plaque-forming cell (PFC) system. Exposure of human peripheral blood lymphocytes to EBV in vitro resulted in an anti-SRBC PFC response in 12 of 16 normal donors. The EBV-induced anti-SRBC PFC response did not require the presence of autologous helper T lymphocytes, but was inhibited by the presence of autologous concanavalin A-generated suppressor T cells. Live virus was required for B-cell activation since the EBV-induced PFC response was inhibited by exposure of EBV to ultraviolet light. Using fluorescent techniques which detected simultaneous intracytoplasmic (ICP) Ig production and the presence of EB nuclear antigen, we found that most, if not all, EBV-activated ICP Ig-positive cells were virally infected. Thus, these studies suggest that viral infection of Ig-producing B lymphocytes is required for EBV-induced polyclonal B-lymphocyte activation. Although the participation of T lymphocytes is not required for the induction of EBV-triggered B-lymphocyte Ig production, activated T lymphocytes can serve as modulators of this response.     

Antigen-reactive cell opsonization: a mechanism of antibody-mediated immune suppression.

Antisera against sheep red blood cells (SRBC) specifically suppressed the direct anti-SRBC plaque-forming cell (PFC) response in mice when passively administered with the antigen. The suppressive activity of mouse and rabbit anti-SRBC sera was found to correlate with anti-SRBC opsonic activity but not with hemagglutination or hemolysin titers. Macrophage depletion of mice, using carrageenan treatment, inhibited antibody-mediated immune suppression. When mice immunized with SRBC were given ¹²⁵I-labeled Udr, radiolabeled spleen lymphocytes were obtained which specifically formed rosettes with SRBC. These radiolabeled antigen-reactive cells (1ARC) were specifically opsonized in mice treated with antigen-antibody complexes but not in mice treated with antigen or antibody alone. These results suggest that antibody-mediated immune suppression may be due to specific opsonization (and subsequent destruction) of ARC in the presence of antigen-antibody complexes.     

Modification of tumor cells by a low dose of Newcastle disease virus

Summary Augmented tumor-specific T cell responses were observed against the high metastatic murine lymphoma variant ESb when using as immunogen ESb tumor cells that had been modified by infection with a low dose of Newcastle disease virus (NDV). Such virus-modified inactivated tumor cells (ESb-NDV) were potent tumor vaccines when applied postoperatively for active specific immunotherapy of ESb metastases. We demonstrate here that immune spleen cells from mice immunized with ESb-NDV contain enhanced immune capacity in both the CD4⁺, CD8^– and the CD4^–, CD8⁺ T cell compartments to mount a secondary-tumor-specific cytotoxic T cell response in comparison with immune cells from mice immunized with ESb. ESb-NDV immune CD4⁺, CD8^– helper T cells also produced more interleukin 2 after antigen stimulation than the corresponding ESb immune cells. There was no participation of either CD4⁺ or CD8⁺ virus-specific cells in the augmented response. The specificity of the T cells for the tumor-associated antigen remaind unchanged. Thus, there is the paradox that the virus-mediated augmentation of the tumor-specific T cell response in this system involves increased T helper activity but does not involve the recognition of viral epitopes as potential new helper determinants.Abbreviations CTL cytolytic T lymphocytes - IL-2 interleukin 2 - rIL-2 recombinant IL-2 - mAb monoclonal antibody - NDV Newcastle disease virus - SSC syngeneic spleen cell     

Alterations in the Immunogenic Properties of Sheep Erythrocytes by Sonic Disruption

A solubilized sheep red blood cell (SRBC) antigen (supernatant fraction obtained by centrifuging 10^7-2 × 10⁸ sonicated SRBC at 6 × 10⁴ g for 30 min [Sup-SRBC]), whose ability to inhibit anti-SRBC plaque formation was 70% of that of the original sonicated SRBC, was unable to elicit a detectable antibody response in either unprimed or SRBC-primed mice. However, Sup-SRBC as well as intact SRBC antigens generated memory for the secondary response, which was transferable to irradiated syngeneic recipients by injection of immune spleen cells. The memory generated by Sup-SRBC involved helper memory for anti-trinitrophenyl group (TNP) response to challenge with TNP-conjugated SRBC. Increase in the helper T cell memory in the spleens of Sup-SRBC-primed mice was also demonstrated by an in vitro culture experiment and by an adoptive cell transfer experiment. In contrast, no detectable B cell memory was generated by Sup-SRBC. Repeated stimulation with Sup-SRBC never induced significant antibody response but reduced the level of memory. A single injection of a low dose (10⁶) of SRBC also failed to induce a definite primary antibody response generating memory for the secondary response. However, repeated stimulation with this dose of SRBC induced a high antibody response and generated good memory. From these results it is suggested that the intact structure of SRBC is required for the activation of B cells, but is not necessary for the stimulation of T cells.     

Regulation of the immune system by synthetic polynucleotides. VII. Suppression induced by pretreatment with poly A:U.

Pretreatment of mouse spleen cells with polyadenylic-polyuridylic acid complexes (poly A:U) either in vivo or in vitro 24 hr prior to addition of antigen, resulted in a substantial time dependent decrease in anti-SRBC PFC. Enhancement was observed 6 hr after poly A:U, while inhibition did not become evident until 24 hr after pretreatment. Inhibition of the PFC response appeared to result from poly A:U activation of a nylon wool adherent, T suppressor cell, capable of diminishing the response of normal spleen cells exposed to antigen on co-culture.     

T cell tolerization in vitro: modulation of helper and suppressor cell activities

This paper analyzes the conditions for in vitro tolerization of purified whole T cell populations and the consequences on helper and suppressor T cell functions. Highly purified splenic T cells from adult DBA/2 mice were incubated in vitro for 24 hr with high doses of trinitrophenyl coupled to human gamma-globulins (TNP-HGG). A profound inhibition of the TNP-specific helper function of these T lymphocytes was observed in a cooperative culture with normal purified splenic B cells and TNP-SRBC as antigen. This state of specific unresponsiveness was maintained after trypsin treatment of the cells, at the end of the 24-hr incubation with the tolerogen. We checked that this procedure removed the vast majority of F23.1 T cell receptor determinants from the cells. This result indicates that T cell receptors for antigen were not merely blocked by the tolerogen. In addition, B cells preincubated with tolerized T cells for 24 hr remained as responsive to TNP as B cells mixed with normal T cells in similar conditions. This demonstrates that the decreased response is not the result of secondary B cell tolerization. In addition, anti-Ia monoclonal antibodies were shown to block the induction of tolerance. We also showed that tolerized T cells significantly decreased the anti-TNP response of normal T and B cells in vitro, whereas the anti-SRBC response in the same cultures was unaffected. When tolerized T cells were separated into Lyt-2- and Lyt-2+ cells, it was found that tolerized Lyt-2- cells had lost about 75% of their helper activity and that Lyt-2+ cells suppressed 70% of the response of a normal T and B cell culture. Thus, in vitro induction of T cell tolerance results in a specific T cell unresponsiveness which is due to both helper T cell inactivation and induction of specific suppressor T cells.     

Antigen-specific and nonspecific mediators of T-cell/B-cell cooperation. VI. Distinct patterns of cross-reactivity by two human gamma-globulin-primed helper T-cell subpopulations.

We have previously characterized the activities, in vitro, of two different helper T-cell subpopulations, primed with human γ-globulin (HGG). One T-cell subpopulation helps the response of B cells to determinants (e.g., haptens) bound to the same antigen to which the T cells are primed (specific help); the other helper T-cell subpopulation responds to the same priming antigen by secreting a nonspecific molecule which helps B-cell responses to erythrocyte antigens co-cultured with the priming antigen (nonspecific help). These subpopulations also differ in their frequency and dose response to antigen, both in vivo and in vitro. They are similarly susceptible to the induction of unresponsiveness to HGG. In order to determine whether these T-cell subpopulations share or differ in their ranges of antigen recognition, we have compared the reaction of these two HGG-primed helper T-cell subpopulations to a number of γ-globulins (γG's) from other species. Plaque-forming cells generated in response to HGG shared little or no cross-reactivity with any of the heterologous (γG's) tested. In contrast, HGG-primed nonspecific helper T cells responded with significant cross-reactivity when challenged in vitro with dog γG, but HGG-primed specific helper T cells did not respond with any such cross-reactivity. No other heterologous γG tested stimulated any significant cross-reactivity from either HGG-primed T-cell subpopulation. Thus, these two T-cell subpopulations differ in their antigenic recognition. Possible explanations of these data include: (i) a difference in receptor specificity; (ii) a difference in the receptor affinity; (iii) a difference in Ia determinants of the two subpopulations.     

Effects of antilymphocyte serum on thymic independent immunity. 1. Lack of immunosuppressive action on the antibody response to E. coli lipopolysaccharide

Previous studies have shown that cellular and humoral antibody production to type III pneumococcal polysaccharide (SSS-III) is not appreciably altered in neonatally thymectomized mice and is enhanced in animals which have been treated with ALS. In order to determine what effect ALS has on the response to another antigen which does appear to require helper T cells, immunity to E. coli 055:B5 has been investigated. BALB/c mice were injected i.p. with 0.25 ml of ALS on days ?1, 0, and +1 relative to the day of immunization (d.0) with a killed E. coli bacterial vaccine. Splenic plaque forming cells (PFC) and serum hemolysin and hemagglutinin titers were determined 6 days later using sheep erythrocytes which had been coated with purified E. coli lipopolysaccharide (LPS). Mice treated with ALS or normal heterologous serum and immunized with an optimal immunogenic dose of bacteria (150 × 10⁶) had similar numbers of splenic PFC and serum antibody titers. No significant immunosuppressive effect was noted over a wide range of antigen (0.015–1500 × 10⁶) although dose related variations were seen. In contrast to its effect on the response to SSS-III, no enhancement was noted. ALS treated mice which had been simultaneously immunized with E. coli and sheep RBC had specific depression of the T helper dependent response to SRBC but not to LPS. The lack of immunosuppressive effect on antibody production to E. coli LPS provides strong evidence that ALS preferentially acts on T lymphocytes. It further indicates that enhancement occurs with some but not all T helper independent antigens.     

Mechanisms of T and B cell collaboration in the in vitro production of anti-DNA antibodies in the NZB/NZW F1 murine SLE model

B/W mice spontaneously develop IgG antibodies to DNA that cause lethal immune nephritis. T and B cell interactions in the in vitro anti-DNA antibody response of B/W mice were investigated, and two distinct families of helper T cells that drive these responses were defined. First, the anti-DNA antibody-forming cell (AFC) response was found to be increased in B/W mice with nephritis and was inhibited with the monoclonal antibody anti-L3T4, suggesting a major role for helper T cells. Purified splenic T cells from mice with nephritis were able to augment both the IgG and the IgM anti-DNA AFC response of young B/W B cells. T helper cells were cloned from spleens of NZB/W F female mice with high titer anti-DNA antibodies and nephritis. The cloned T cells augmented both IgG and IgM anti-DNA AFC responses of young B/W B cells. Four clones--27.9, 30.7, 30.8, and 30.10--were selected for further study. These cells proliferated, in the context of syngeneic (H2d/z) antigen-presenting cells (APC) but not to allogeneic APC. Analysis of the mechanism of T helper cell clone-mediated augmentation of anti-DNA AFC revealed two populations: "cognate" T helper cells, which specifically augment anti-DNA AFC (30.7 and 30.10), and non-antigen-specific T helper cells (27.9 and 30.8), which augment the response of B cells of differing specificity by a bystander mechanism, probably through increased release of B cell growth and differentiation factors.     

Increased proline transport resulting from growth of normal and Kirsten sarcoma virus-transformed BALB 3T3 cells in the presence of N(6), O(2')-dibutyryl cyclic adenosine 3',5'-monophosphate.

Proline transport in Kirsten sarcoma virus-transformed BALB 3T3 (Ki-3T3) cells was increased approximately twofold by 0.5 mm dibutyryl cAMP (dbcAMP), and the increase was observed whether transport was assayed in the presence or absence of cycloheximide. Two days of exposure to the analog was required for maximum stimulation. Increased proline transport contributed almost entirely to the increased incorporation of [¹⁴C]proline into noncollagen protein but for only 13% of the increased incorporation into collagen of dbcAMP-treated Ki-3T3 cells. Proline transport was further characterized using an assay system containing 0.1 mm cycloheximide, which did not affect transport over a 30-min period. The K_m for proline was decreased from 6.5 to 3.4 mm by dbcAMP treatment of Ki-3T3. Proline transport in Ki-3T3 proceeds almost entirely via the A system, and the effect of dbcAMP appears to be on this system specifically since glycine and glutamine transport, which are heterogeneous, were not affected but transport of N-methylaminoisobutyrate, a specific A system substrate, was increased by dbcAMP treatment. Although 0.5 mm butyrate increased proline transport in Ki-3T3 cells to a similar degree as dbcAMP, the effect of the latter appeared related to its action as a cAMP analog since N⁶-monobutyryl cAMP, having a stable butyryl group, and 8-bromo-cAMP also increased proline transport while dbcGMP did not. The rate of proline transport in normal BALB 3T3 cells was only 30–40% lower than that of Ki-3T3 cells at various growth stages, and dbcAMP and 8-bromo-cAMP treatment also increased proline transport in the normal cells. The results of these studies suggest that dbcAMP and other cAMP analogs induce the synthesis of an altered component of the A system for amino acid transport and that the effect of these compounds is unrelated to the effect of transformation on proline transport.     

The effects of corticosteroids on immunoregulation in sarcoidosis.

The effects of in vivo hydrocortisone administration on the kinetics and functional capabilities of cells involved in the immune response in sarcoidosis were examined. Untreated sarcoidosis patients have a decrease in the absolute numbers of circulating T lymphocytes (P < 0.05). However, with regard to the proportions of T lymphocyte subpopulations, there is an increase in the relative proportions of IgG Fc receptor positive T cells (T_G) (P < 0.01), which have suppressor capabilities in certain in vitro systems of mitogen-induced antibody production, and a relative decrease in IgM Fc receptor positive T lymphocytes (T^M) which have helper effects in this system (P < 0.05). Additionally, sarcoidosis patients have circulating “suppressor” monocytes capable of suppressing anti-sheep red blood cell (SRBC) plaque-forming cell (PFC) responses by pokeweed mitogen (PWM)-stimulated lymphocytes. The in vitro removal of this cell abrogated this depressed response (P < 0.01). Intravenous administration of hydrocortisone produced a transient absolute T lymphocytopenia (P < 0.01) accompanied by a relative increase in T^G cells (P < 0.01) and a relative decrease in T_M cells (P < 0.02). Four hours after hydrocortisone therapy, at the point of maximal hydrocortisone-induced monocytopenia (P < 0.01), the suppressed ability of sarcoidosis lymphocytes to synthesize and secrete in vitro anti-SRBC antibody after polyclonal activation was corrected (P < 0.01), and PFC responses comparable to those seen in untreated normal subjects were obtained. These studies demonstrate that corticosteroid administration has profound effects on certain in vitro demonstrable immunoregulatory abnormalities in sarcoidosis.     

Human C3a-mediated suppression of the immune response. I. Suppression of murine in vitro antibody responses occurs through the generation of nonspecific Lyt-2+ suppressor T cell

C3a derived from the third component of human complement was found to suppress in vitro murine anti-SRBC responses. C3a-mediated suppression occurs through the generation of nonspecific Lyt-2+ suppressor T cells. The generation of suppressor cells occurs at an early phase in the response because incubation of naive T cells with C3a for as little as 30 min results in suppression of the anti-SRBC response. The generation of suppressor T cells requires the interaction of T cells, C3a, and a Sephadex G-10-adherent cell, presumably a macrophage. Although the mechanism of action of these suppressor cells has not been elucidated, several possibilities have been eliminated. C3a-suppressor T cells do not apparently release inhibitory lymphokines, nor is helper cell activity inhibited by a 2-day co-culture with these suppressor cells. The observation that interleukin 2 (IL 2)-containing lymphokine preparations could overcome C3a-induced suppression led us to investigate the interaction of the suppressors with IL 2 producer cells. However, neither C3a nor C3a-generated suppressor T cells can block the synthesis of IL 2.     

Immunological properties of Fc receptor on lymphocytes. 1. Functional differences between Fc receptor-positive and negative lymphocytes in humoral immune responses.

Using an EA rosetting system, it was observed that Fc receptors (FcR) were present on the surface of T cells as well as B cells, and that functional differences existed between FcR-positive (FcR⁺) and FcR-negative (FcR^?) cells in both T and B cells in in vivo humoral immune responses. Approximately 15% of splenic T cells obtained by nylon wool passage are FcR⁺. The number of surface immunoglobulinbearing cells as detected by immunofluorescent staining accounted for less than 10% of these FcR⁺ cells. FcR⁺ and FcR^? T+B-cell populations obtained from spleens contain 60 and 20% of surface immunoglobulin-positive cells, respectively. In the adoptive primary response in which horse RBC and dinitrophenyl-conjugated dextran (DNP-DE) were used as T-dependent and T-independent antigens, respectively, the majority of precursor B cells were FcR^?. In the secondary response using hapten-primed B cells and carrier-primed T cells, the majority of memory B cells for a haptenic determinant were also FcR^?. Furthermore, the majority of functional cells exerting helper activity in the same hapten-carrier system are FcR^? cells, and FcR⁺ T cells collaborate much less effectively with either memory B cells or helper FcR^? T cells.