Direct demonstration of specific suppressor T cells in the mice tolerant to type III pneumococcal polysaccharide: two-step requirement for development of detectable suppressor cells

Spleen cells from CAF1 mice made tolerant to type III pneumococcal polysaccharide (S3) with S3 coupled to syngeneic spleen cells (S3-SC) develop S3-specific suppressor T cells (Ts). These Ts could be demonstrated consistently only when spleen cells from tolerant mice were cultured in vitro with the specific antigen and the specific tolerogen. Spleen cells from normal mice cultured under the same conditions did not suppress the antibody response to S3. When different numbers of Ts were transferred to normal CAF1 mice, an unusual dose-effect pattern was observed. Maximal suppression of the S3 response occurred when relatively low numbers of Ts, 3 to 30 x 10(5) per recipient, were transferred, whereas larger numbers of cells, 150 x 10(5) per recipient, were not suppressive. These results indicate that a presumably T-independent antigen, S3, can activate antigen-specific Ts. These Ts exhibit unusual dose effects upon transfer and require both an in vivo induction period and in vitro activation for development of maximal activity. These latter observations suggest that S3 may activate a different population of T cells with suppressor function than do conventional T-dependent antigens. The loss of suppression observed when greater than optimal numbers of cells were transferred suggests that a second type of T cell, which has the ability to 'neutralize' the activity of S3-specific Ts, is also induced in the same spleen cell population.     

Regulation of the murine IgE antibody response. I. Characterization of suppressor cells regulating both persistent and transient responses and their sensitivity to low doses of X-irradiation.

Anti-ovalbumin (OA) IgE antibody responses were measured in B6D2F1 mice as a function of time and antigen dose. One hundred to 200 microgram of OA in Al(OH)3 elicited transient responses, whereas 1 to 10 microgram of OA in Al(OH)3 elicited persistent anti-OA IgE responses of high titer. T cells isolated from the spleens of mice mounting either a persistent or a transient response strongly suppressed primary anti-DNP IgE responses in unirradiated recipient mice that were immunized with DNP-OA in Al(OH)3; it was, therefore, concluded that suppressor T cells (Ts cells) were activated during both the persistent and transient IgE responses. Nevertheless, in the present study it was not possible to completely rule out the contention that IgG antibodies may also have been suppressing the IgE response. With a modified adoptive transfer system, it was shown that these Ts cells were sensitive to low doses (250 R) of x-irradiation. The suppressive activity of long-term OA primed cells was also shown to be markedly enhanced when cultured for 24 hr with soluble OA; this finding was interpreted to indicate the presence of memory suppressor cells.     

Induction of T cell responses in nonresponder mice by abolishing suppression with monoclonal antibodies recognizing A region-controlled, T cell-specific determinants

Mouse strains carrying the kappa allele at loci A beta, A alpha, E beta, and E alpha are nonresponders to lactate dehydrogenase B (LDHB) and to allotypic determinants of IgG2a myeloma proteins (for example, UPC10 used in this study). The nonresponsiveness to these antigens is caused by T suppressor (Ts) cells that prevent antigen-primed T helper (Th) cells from proliferating. We demonstrate here that monoclonal antibodies specific for an A region-controlled molecule selectively expressed on T cells (A-T) are capable of inducing anti-LDHB and anti-UPC10 responses of primed T cells from nonresponder strains. A monoclonal anti-J antibody that cross-reacts with the A-T molecule also induces responsiveness, whereas another J-specific antibody that lacks this cross-reactivity fails to do so. The mechanism of response induction is blocking of the interaction between the Ts cell or its factor (TsF) and the target of suppression, the antigen-specific Lyt-1+2- (Th) cell. The blocking occurs at the level of the Ts cell and the TsF. The data indicate that Ts cells and TsF carry a unique, A region-controlled molecule that is not only functionally analogous but also serologically similar to the J molecule.     

Requirements for activation of contrasuppressor T cells by type III pneumococcal polysaccharide

Either S3-coupled spleen cells (S3-SC) or soluble S3 activates two populations of regulatory T cells, T suppressor cells (Ts) and contrasuppressor T cells (Tcs). The latter cells function to mask the activity of Ts in unfractionated T cell populations, so that Ts can be detected only after removal of Tcs. Activation of Tcs by S3 may be required for induction of an antibody response to S3. This is suggested by the findings that Tcs are activated only by immunogenic doses of S3, that Tcs are not detectable in the spleens of mice tolerant to S3, and that (CBA/N X BALB/c)F1 male (xid) mice, which are genetically unresponsive to S3, do not develop Tcs after immunization with S3. Moreover, the kinetics of activation of Tcs by S3 closely parallels the kinetics of the antibody response to S3. Tcs have no detectable activity in the absence of Ts, indicating that these cells do not function as amplifier or helper T cells.     

Functional analysis of cloned macrophage hybridomas. VI. Differential ability to induce immunity or suppression

We previously screened a series of macrophage hybridomas derived from fusion of P388D1 (H-2d) tumor cells with CKB (H-2k) splenic adherent cells for their ability to induce I-J restricted Ts cell responses. One Ia+ macrophage clone (63) consistently induced Ag-specific, I-J-restricted Ts. To evaluate whether macrophage hybridoma 63 also induced delayed-type hypersensitivity (DTH) immunity, mice were immunized with hapten-coupled macrophage hybridoma cells. Hapten-coupled splenic adherent cells and control macrophage hybridomas induced significant primary DTH responses, whereas hapten-coupled macrophage 63 induced little or no immunity when injected into H-2 compatible hosts. However, macrophage hybridoma 63 specifically activated I-Ak, I-Ad, or I-Ed restricted T cell hybridomas/clones, in vitro in the presence of appropriate Ag. Three different strategies designed to eliminate suppressor cell activity were successfully used to demonstrate that hapten-coupled macrophage 63 could also induce in vivo immunity. First, after immunization with hapten-coupled macrophages, mice were treated with cyclophosphamide. Second, macrophage 63 was treated with anti-IJ idiotype antibody before 4-hydroxy-3-nitrophenyl acetyl hapten (NP) coupling. Finally, haptenated macrophages were injected into I-A compatible but I-J incompatible recipients. These protocols are known to inhibit the induction of Ts activity, thus these results indirectly suggest that there is stimultaneous generation of Ts activity in vivo. The latter hypothesis was tested in adoptive transfer experiments. Transfer of lymph node cells from NP-63 primed B10.BR (H-2k) mice induced immunity in naive 4R animals, whereas the same number of immune cells suppressed NP-induced DTH responses in 5R mice. The combined results indicate that a cloned macrophage line can activate both Th and Ts cells. Macrophages which induce Ts activity may be responsible for maintaining the balance of immunity vs suppression. The data support the hypothesis that IJ interacting molecules (IJ-IM) expressed on macrophages are critical for induction of suppressor cell activity.     

The nature of the interaction between suppressor and helper T cells in the response to LDHB

Purified Lyt-1+2+ T cells were depleted of alloreactive cells by BUdR and light treatment, and then were primed in vitro against LDHB presented on allogeneic APC. Such cells could be restimulated by LDHB on the same allogeneic APC, but not by LDHB on APC syngeneic with the T cells. The restimulated T cells suppressed the proliferative response of Lyt-1+2- T cells primed and restimulated by the same antigen. The suppression, which was antigen specific, occurred after a 6-hr co-culture of the suppressor (Tse) and proliferating helper (Th) cells. The successful interaction (as measured by suppression) between allogeneic Th and Tse cells was found to be determined by the restriction specificity but not the MHC haplotype of Th cells, and the MHC haplotype but not the restriction specificity of Tse cells. Thus, suppression occurred only when the Tse cells carried genes controlling the MHC molecules that served as restriction elements for antigen recognition by the Th cells. No evidence could be obtained for the participation of APC in the Tse-Th interaction. The data suggest the interaction is based on the recognition by the Th cell of the antigen presented in the context of MHC molecules controlled by the Tse cell.     

Antigen-specific T cell-mediated suppression. II. In vitro induction by I-J-coded L-glutamic acid50-L-tyrosine50 (GT)-specific T cell suppressor factor (GT-T8F) of suppressor T cells (T82) bearing distinct I-J determinants.

The induction of new suppressor T cells (Ts2) by suppressive extracts (TsF) from L-glutamic acid50L-tyrosine50 (GT) nonresponder mice was examined. Incubation of normal spleen cells with allogeneic GT-TsF for 2 days in vitro led to the generation of Ts2 cells able to suppress subsequent responses to the immunogen GT-methylated bovine serum albumin (GT-MBSA) in vivo. This induction occurred efficiently when TsF donor and target cells differed at all of H-2, including the I-J subregion. B10.BR (H-2k) GT-TsF, adsorbed on, then acid eluted from GT-Sepharose and anti-I-Jk [B10.A (3R) anti-B10.A (5R)]-Sepharose in a sequential fashion could induce BALB/c (H-2d) spleen cells to become Ts2 only if nanogram quantities of GT were added to the purified GT-TsF. This indicates a requirement for a molecule or molecular complex possessing both I-J determinants and antigen (GT)-binding specificity, together with GT itself, for Ts2 induction. The induced Ts2 are I-J+, since their function can be eliminated by treatment with anti-I-Jk plus C. These I-J determinants are coded for by the precursor of the Ts2 and do not represent passively adsorbed, I-J coded TsF, since anti-Ijk antiserum [(3R X DBA/2)F1 anti-5R] which cannot recognize the BALB/c (I-Jd) TsF used for induction still eliminates the activity of induced A/J (I-Jk) Ts2. These data provide further evidence for and information about the minimum of two T cells involved in antigen-specific suppressor T cell systems.     

Epidermal cells in activation of suppressor lymphocytes: further characterization

Intravenous administration of hapten-coupled, high-density (density greater than 1.077) epidermal cells (HD-EC) to mice results in the appearance of transferable splenic T suppressor (Ts) cells as assayed in adoptive transfer experiments. Depletion of I-A bearing cells from the HD-EC population before hapten coupling prevents these cells from inducing Ts cell formation, whereas depletion of Thy-1-bearing cells from the HD-EC cell preparation has no effect. When HD-EC are adhered to glass for 2 hr, the ability to induce Ts cell formation resides in the adherent population. Exposure of HD-EC to a dose of ultraviolet radiation (UVR) that largely abrogates the ability of hapten-coupled EC to immunize mice for a DTH response does not affect the ability of these cells to activate Ts cells. Treatment of mice with i.p. administration of 20 mg/kg of cyclophosphamide 2 days before EC harvesting abrogates the ability of HD-EC from these mice to induce Ts cell formation. HD-EC from B10.A(3R) (I-Jb) but not B10.A(5R) (I-Jk) mice induce Ts cell formation in B10.A(3R) mice, demonstrating that the ability to do so is restricted by the I-J locus. Transmission electron microscopy of adherent HD-EC populations demonstrated that two cell types were present. One type had the characteristics of keratinocytes; the other was monocyte-like and resembled Langerhans cells or indeterminate cells in many aspects. Immunoelectron microscopy revealed this second cell type to bear I-A/I-E antigen. These cells were T-200 positive and Mac-1 negative by immunoperoxidase staining. Extensive examination by light and electron microscopy failed to reveal any dermal components in the EC populations; however, a very small degree of dermal contamination cannot be excluded. Thus, EC that activate afferent-acting Ts cells are high-density, I-A+, Thy-1-, I-J restricted, glass adherent, and functionally UVR resistant and cyclophosphamide sensitive.     

Clonal analysis of autoreactive B cells in a murine model of autoimmune hemolytic anemia

Hybridoma technology was used to examine the repertoire of autoantibody producing B cells in mice with autoimmune hemolytic anemia induced by injection of rat red blood cells (RBC). The results point to the importance of suppressor T cells (Ts) in both the induction as well as the maintenance of the self-specific B-cell repertoire at the clonal level. Thus when normal BALB/c mice were immunized to provoke a high autoantibody response, the hybrids generated were mainly (97%) cross-reactive with mouse RBC, whereas after immunization to elicit Ts and a low autoantibody response, hybrids were mainly (87%) rat RBC specific. In addition, when hybrids were generated from rat RBC immunized (CBA X B10A)F1 mice, in which Ts levels had been depleted during ontogeny, hybrids with "forbidden" purely anti-self (mouse RBC) specificity were detected.     

Importance of suppressor T cells in cyclophosphamide-induced tolerance to the non-H-2-encoded alloantigens. Is mixed chimerism really required in maintaining a skin allograft tolerance?

Mechanisms of cyclophosphamide (CP)-induced tolerance were studied. When AKR/J Sea (AKR: H-2k) mice were primed i.v. with 5 x 10(7) spleen cells plus 1 x 10(7) bone marrow cells from [C57BL/6 Slc (B6; H-2b) x C3H/He Slc (C3H; H-2k)]F1 (B6C3F1) mice and treated i.p. with 200 mg/kg CP 2 days later, the survival of C3H skin was moderately prolonged, but the survival of either B6 or B6C3F1 skin was not prolonged. By this treatment, however, mixed chimerism of B6C3F1 cells in the AKR mice was not established. When C3H cells were used as the tolerogen, a minimal degree of mixed chimerism associated with profound tolerance to C3H skin was established. Similar results were observed in various donor-recipient combinations. When C3H skin was grafted in the AKR mice 12 wk after the treatment with C3H cells and CP, or B6C3F1 cells and CP, survival of the grafted C3H skin was prolonged remarkably or moderately, respectively, although mixed chimerism was not detectable at the timing of grafting in either of the groups. In this late stage of tolerance, a strong level of tolerogen-specific suppressor cell activity was observed in those tolerant AKR mice. The suppressor activity was mainly attributable to T cells. These results suggest that the role of Ts cells in order to maintain skin tolerance is important in our CP-induced tolerance system, especially in the late stage of tolerance. Moreover, the generation of the Ts cells does not necessarily require the establishment of a long term mixed chimeric state.     

The molecular basis of alloreactivity in antigen-specific, major histocompatibility complex-restricted T cell clones

We have studied the relationship between major histocompatibility complex (MHC)-restricted antigen recognition and alloreactivity by examining T cell receptor (TCR) alpha and beta gene expression in cytochrome c-specific, Ek alpha:Ek beta (Ek)-restricted helper T cell clones derived from B10.A mice. The clones could be segregated on the basis of four distinct alloreactivity patterns. Clones cross-reactive for three different allogeneic la molecules (As alpha:As beta [As], Ab alpha:Ab beta [Ab], Ek alpha: Eb beta [Eb]) expressed the same V alpha and V beta gene segments, generating the distinct alloreactive specificities via unique V alpha-J alpha and V beta-D beta-J beta joining events. Ek alpha:Es beta (Es)-alloreactive B10.A clones expressed the same V alpha, J alpha, and V beta segments as an Es-restricted, Ek-alloreactive, cytochrome c-specific, H-2-congenic B10.S(9R) clone. This homology between TCRs mediating allorecognition of la molecules and recognition of the same la molecules as restriction elements associated with nominal antigen suggests that MHC-restricted recognition and allorecognition represent differences in the affinity of the TCR-MHC molecule interaction.     

Regulation of cell-mediated immunity in cryptococcosis. II. Characterization of first-order T suppressor cells (Ts1) and induction of second-order suppressor cells

Cryptococcosis patients frequently have high levels of cryptococcal antigen in their body fluids, and the levels of circulating antigen can generally be used to predict the patient's recovery, with high or rising antigen titers indicating a poor prognosis and low or decreasing levels a good prognosis. In a previous study, we reported on a murine model for studying the effects of cryptococcal antigen on host defense mechanisms. In that work, we demonstrated that an i.v. injection of cryptococcal antigen (CneF) into CBA/J mice, to simulate the antigenemia known to occur in human cryptococcosis, induced a population of T suppressor cells (Ts1) in the lymph nodes (LN). Upon adoptive transfer, the Ts1 cells specifically suppressed the afferent limb of the delayed-type hypersensitivity (DTH) response to cryptococcal antigen. In the present study, we show that the precursors of the Ts1 cells are sensitive to low-dose cyclophosphamide treatment and that the phenotype of the Ts1 cells is Lyt-1+, Ia+ (I-J+). LN cells from CneF-injected mice or a soluble factor derived therefrom can induce in the spleens of recipient mice a second-order suppressor cell population that suppresses the efferent limb of the DTH response. The cells that induce the second-order or efferent suppressor cells have the same phenotype as the cells that appear to suppress the afferent limb of the DTH response. The findings in this study indicate that a complex regulatory mechanism is responsible for the observed suppression of the DTH response in this infectious disease model. Furthermore, the suppressive circuit thus far defined for cryptococcal antigen is similar to the antigen-specific suppressor cell pathway outlined for certain chemically defined haptenic systems.     

Ek beta mutant antigen-presenting cell lines expressing altered Ak alpha molecules

Antigen-presenting cells (APC) expressing mutant Ek beta and Ak alpha proteins were isolated after chemical mutagenesis of TA3 cells and negative immunoselection for altered Ek beta molecules. Mutant clones were analyzed for biosynthesis, assembly, and cell surface expression of altered Ia molecules, and were assayed for antigen-presenting function by using a variety of T cell clones. Three types of mutants were detected: type 1, which had lost expression of the Ek beta chain and produced altered Ak alpha chains; type 2, which also expressed altered Ak alpha chains, and which expressed Ek beta proteins that had lost reactivity to the 17.3.3 and 74D monoclonal antibodies (mAb), but retained reactivity to other anti-Ek beta mAb; and type 3, which had lost expression of both Ek beta and Ak beta: Ak alpha surface molecules. Thus, all of the mutant clones that produced modified Ak alpha proteins also displayed either total loss or serologic modification of the Ek beta molecule. Ek beta:E alpha-reactive T cell clones were not stimulated when type 1 or type 3 cells were used as APC, but all such T cells were fully reactive with type 2 mutant APC. Most Ak beta:Ak alpha-reactive T cell clones could respond to type 1 and 2 APC, and none were responsive to type 3 APC. However, two autoreactive Ak beta:Ak alpha-specific T cell hybridomas were stimulated only very weakly by type 1 and type 2 cells expressing modified Ak alpha proteins. These results demonstrate that Ia mutations can have highly selective effects on antigen presentation to T cells as well as on mAb binding, and thus suggest that individual Ia molecules may be composed of many different functional subsites.     

Arsonate-specific murine T cell clones. IV. Properties of I-E- and I-A-restricted clones

The T cell antigen L-tyrosine-p-azobenzenearsonate is unique in being a simple determinant that can be presented in the context of both I-A and I-E. I-E-restricted T cell clones derived from B10.A(5R) mice were found to fall into three groups: Type I clones recognized antigen only in the context of syngeneic apcs, Type II clones recognized antigen with the same highly specific major histocompatibility complex restriction but in addition proliferated in response to allogeneic stimuli; Type III clones were "degenerate" in their major histocompatibility complex-restricted recognition of antigen and proliferated when antigen-presenting cells bearing Eb beta Ek alpha (syngeneic), Ek beta Ek alpha, or Ed beta Ed alpha were used. These observations allow some conclusions to be drawn about sites on the I-E molecule that may be functionally significant in the presentation of this antigen. By using the B cell hybridoma LK35.2 as target cells, some of these T cell clones act as cytotoxic cells in the Class II-restricted manner predicted from the results of proliferative assays. Class II-restricted cytotoxicity can therefore be controlled by both I-A and I-E mouse Ir gene loci.     

Susceptibility to polyomavirus-induced tumors in inbred mice: role of innate immune responses

Mice of the PERA/Ei strain (PE mice) are highly susceptible to tumor induction by polyomavirus and transmit their susceptibility in a dominant manner in crosses with resistant C57BR/cdJ mice (BR mice). BR mice respond to polyomavirus infection with a type 1 cytokine response and develop effective cell-mediated immunity to the virus-induced tumors. By enumerating virus-specific CD8(+) T cells and measuring cytokine responses, we show that the susceptibility of PE mice is due to the absence of a type 1 cytokine response and a concomitant failure to sustain virus-specific cytotoxic T lymphocytes. (PE x BR)F(1) mice showed an initial type 1 response that became skewed toward type 2. Culture supernatants of splenocytes from infected PE mice stimulated in vitro contained high levels of interleukin-10 and no detectable gamma interferon, while those from BR mice showed the opposite pattern. Differences in the innate immune response to polyomavirus by antigen-presenting cells in PE mice and BR mice led to polarization of T-cell cytokine responses. Adherent cells from spleens of infected BR mice produced high levels of interleukin-12, while those from infected PE and F(1) mice produced predominantly interleukin-10. PE and F(1) mice infected by polyomavirus responded with increases in antigen-presenting cells expressing B7.2 costimulatory molecules, whereas BR mice responded with increased expression of B7.1. Administration of recombinant interleukin-12 along with virus resulted in partial protection of PE mice and provided complete protection against tumor development in F(1) animals.     

Immunoregulation of lysozyme-specific suppression. III. Epitope-specific amplification of immunosuppression induced by monoclonal suppressor-T-cell products

The hen egg-white lysozyme (HEL)-specific suppression induced by soluble molecules produced by a monoclonal T-cell lymphoma line (LH8-105) obtained from HEL-specific suppressor T lymphocytes has been examined. Injection of I-J+ molecules from LH8-105 cell culture supernatant (TsFa) in HEL-primed mice during the afferent phase of the response induced Lyt-2+ second order suppressor T (Ts) cells which, upon transfer into HEL-CFA-primed syngeneic recipients, inhibit the delayed-type hypersensitivity (DTH) response to HEL. Transfer of spleen cells from TsFa-injected mice primed with HEL or human lysozyme suppresses the DTH response to HEL in recipient mice whereas this response is not affected by cell transfer from ring-necked pheasant egg-white lysozyme (REL)-primed and TsFa-injected mice, indicating that induction of second order Ts by TsFa is specific for a lysozyme epitope including phenylalanine at position 3. Fine antigenic specificity of second order Ts-cell induction is confirmed by similar results obtained upon injection of TsFa in mice primed with HEL N-terminal synthetic peptide or with an analog in which, as in REL, phenylalanine has been substituted by tyrosine at position 3. The same fine antigenic specificity observed in the induction of second order Ts cells is also present in the expression of TsFe suppressive activity. The similar antigenic specificity of Tsa and Tse suggests that Tse cells could result from amplification of the Tsa cell population or these two cell subsets could reflect different maturation stages of the same cell type rather than distinct T-cell populations activated in cascade.     

T cell-induced Ig allotypic suppression in mice. II. Both CD4+ CD8- and CD4- CD8+ T cell subsets from sensitized Igha mice are required to induce suppression of Igh-1b allotype expression

We established the phenotype of T splenocytes (Ts) from Igha/a BALB/c mice sensitized against B splenocytes from the Ighb/b CB20 congenic mice that induce Igh-1b (IgG2a of the Ighb haplotype) suppression. This was achieved by studying the action of anti-T cell subset mAb on the capacity of Ts to induce this chronic allotypic suppression in Igha/b (BALB/c x CB20)F1 mice. The Ts were treated with cytotoxic anti-mouse CD4 or anti-mouse CD8 rat mAb in vitro before their injection into the Igha/b newborns or in vivo after their injection into the Igha/b newborns. Exposure to either anti-CD8 or anti-CD4 mAb in vitro or in vivo leads to loss of the capacity of Ts to induce Igh-1b allotypic suppression. Mixing CD4+-cell-depleted Ts and CD8+-cell-depleted Ts preparations restored the capacity of the cells to induce Igh-1b suppression. Thus, both CD4+ CD8- Ts and CD4- CD8+ Ts are required for the induction of this allotypic suppression. Bone marrow cells and B splenocytes from Igh-1b-suppressed adult Igha/b mice were shown to be able to durably express Igh-1b when transferred into irradiated Igha/a BALB/c hosts whereas whole spleen cells from such donors failed to do it. Abrogation of Igh-1b suppression by in vivo anti-CD8 mAb treatment was achieved in adult Igha/b heterozygotes but with a lower efficiency than in adult Ighb/b homozygotes, all being chronically Igh-1b suppressed. The CD4- CD8+ cell population essential for maintaining this suppression is resistant to in vivo 600 rad irradiation and seems to be slightly inhibited by in vivo administration of free Igh-1b.     

Altered colonizing ability for mouse large intestine of a surface mutant of a human faecal isolate of Escherichia coli

Escherichia coli F-17 Sr a human faecal isolate, is resistant to the T-series of bacteriophages (i.e. T2 to T7). A T2-sensitive mutant of E. coli F-17 Sr was isolated following acriflavin treatment. This mutant, E. coli F-17 Sr Ts was found to be sensitive to the entire T-series of phages. E. coli F-17 Sr and E. coli F-17 Sr Ts did not differ quantitatively in total LPS content. However, analysis of LPS revealed that a large fraction of E. coli F-17 Sr Ts was devoid of O-side-chains. This accounted for the sensitivity of this strain to bacteriophages T3, T4, and T7. In addition, E. coli F-17 Sr Ts contained only about half the amount of capsular material contained by E. coli F-17 Sr accounting for the sensitivity of the mutant to bacteriophages T2, T5, and T6. Although the two strains colonized equally well when fed individually to streptomycin-treated mice, when fed simultaneously to streptomycin-treated mice, E. coli F-17 Sr Ts colonized at a level of about 1 x 10(8) cells (g faeces)-1, whereas E. coli F-17 Sr colonized at only 1 x 10(4) cells (g faeces)-1. These studies suggest that bacterial cell surface components modulate the large intestine colonizing ability of E. coli F-17 Sr in the mouse large intestine.     

创伤小鼠血清,巨噬细胞,Ts细胞对反抑制T细胞的影响

研究了创伤小鼠反抑制T细胞(Tcs)比例、功能的变化及创伤血清、巨噬细胞、抑制性T细胞(Ts)对正常小鼠Tcs细胞的影响。结果表明,创伤小鼠脾细胞中VVL~ 细胞百分率于伤后一过性减少,Tcs细胞在T淋转、IL-2、IL-2R检测系统中的反抑制活性均明显受抑;创伤小鼠血清、巨噬细胞、Ts细胞在体外对正常Tcs细胞反抑制活性(T淋转、IL-2、IL-2R检测系统)均具有不同程度的抑制作用,创伤后4天小鼠血清在体内对正常小鼠脾脏VVL~ 细胞百分率无明显影响,但可明显降低正常小鼠Tcs细胞的反抑制活性。表明创伤可致Tcs细胞比例及功能发生改变,创伤后血清、巨噬细胞、Ts细胞参与介导了Tcs细胞功能的受抑过程。     

Absence of suppression in natural and induced tolerance to F antigen

The role of suppression in natural and induced tolerance to F antigen was investigated in two sets of experiments. In the first, CBA mice were submitted to pretreatments which decrease suppression and the antibody response to self- or allo-F type was investigated. The second set of experiments involved the transfer of spleen cells from tolerized or from naturally tolerant mice into normal mice which were then primed with allo-F, as well as the co-transfer of tolerant and primed lymphocytes into normal mice, to test whether tolerant lymphocytes present suppressor cells. The results indicate that the immune response against allo-F antigen is normally kept in a low level by a suppressive mechanism, and that F-specific suppressor T cells are absent from tolerant mice.Abbreviations used in this paper ATx adult thymectomy - BSS buffered salt solution - CFA Freund's complete adjuvant - CY cyclophosphamide - F.1 type-1 F antigen - F.2 type-2 F antigen - PBS phosphate-buffered saline - RIA radioimmunoassay - Th T helper cell - Ts T suppressor cell