scholarly journals The involvement of suppressor T cells in Ir gene regulation of secondary antibody responses of primed (responder X nonresponder)F1 mice to macrophage-bound L-glutamic acid60-L-alanine30-L-tyrosine.

1978 ◽  
Vol 148 (5) ◽  
pp. 1324-1337 ◽  
Author(s):  
R N Germain ◽  
B Benacerraf
Keyword(s):  
T Cells ◽  
Antigen Presentation ◽  
Cell Activity ◽  
Suppressor Cell ◽  
Similar Data ◽  
Spleen Cells ◽  
Suppressor T Cells ◽  
Additional Support

(Responder [R] X nonresponder [NR])F1 mice give indistinguishable primary in vitro plaque-forming cell (PFC) responses to either R or NR parental macrophages (Mphi) pulsed with the Ir-gene controlled antigen L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT). However, such (R X NR)F1 mice, if primed to GAT, retained in vitro responsiveness to GAT-R-Mphi, but no longer responded to GAT-NR-Mphi. This suggested (a) a possible Mphi-related locus for Ir gene activity in this model, and (b) the occurrence of active suppression after priming with GAT leading to a selective loss of the usual primary responsiveness of (R X NR)F1 mice to GAT-NR-Mphi. This latter interpretation was tested in the current study. [Responder C57BL/6 (H-2b) X nonresponder DBA/1 (H-2q)]F1 mice were primed with 100 microgram GAT in pertussis adjuvant. 4-8 wk later, spleen cells from such mice were tested alone or mixed with normal unprimed F1 spleen cells for PFC responses to GAT-R-Mphi and GAT-NR-Mphi. The primed cells failed to respond to GAT-NR-Mphi, and moreover, actively suppressed the normal response of unprimed F1 cells to GAT-NR-Mphi. If the primed spleen cell donor had been treated with 5 mg/kg cyclophosphamide 3 days before priming or with 5-10 microliter/day of an antiserum to the I-Jb subregion [B10.A(5R) anti B10.A(3R)] during the first 4 days postpriming (both procedures known to inhibit suppressor T-cell activity), cells from such mice responded in secondary culture to both GAT-R-Mphi and also GAT-NR-MPhi. In addition, such spleen cells no longer were capable of suppressing normal F1 cells in response to GAT-NR-Mphi. Similar data were obtained using [CBA (H-2k) X DBA/1 (H-2q)]F1. Further, it was shown that (a) primary responsiveness to GAT-NR-Mphi was not an artifact of in vitro Mphi pulsing, because in vivo GAT-pulsed Mphi showed the same activity and (b) the secondary restriction for Mphi-antigen presentation was controlled by H-2 linked genes. These data suggest an important role for suppressor T cells in H-2 restricted secondary PFC responses, and also provide additional support for the hypothesis that Ir-gene controlled differences in Mphi antigen presentation are related to both suppressor cell generation and overall responsiveness in the GAT model.

scholarly journals Antigen-specific suppressor T-cell activity in genetically restricted immune spleen cells.

1978 ◽  
Vol 148 (5) ◽  
pp. 1271-1281 ◽  
Author(s):  
C W Pierce ◽  
J A Kapp
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Activity ◽  
Antibody Responses ◽  
Spleen Cells ◽  
Suppressor T Cells ◽  
Specific Suppressor T Cells ◽  
Immune Spleen Cells

Virgin spleen cells develop comparable primary antibody responses in vitro to syngeneic or allogeneic macrophages (Mphi) bearing the terpolymer L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT), whereas immune spleen cells primed with syngeneic or allogeneic GAT-Mphi develop secondary responses preferentially when stimulated with GAT-Mphi syngeneic to the GAT-Mphi used for priming in vivo. These restrictions are mediated by products of the I-A subregion of the H-2 complex and are operative at the level of the GAT-Mphi-immune helper T-cell interactions. To investigate why these immune spleen cells fail to develop a significant antibody response to GAT-Mphi other than those used for in vivo immunization and determine the mechanism by which the restriction is maintained, spleen cells from virgin and syngeneic or allogeneic GAT-Mphi-primed mice were co-cultured in the presence of GAT-Mphi of various haplotypes. Antibody responses to GAT developed only in the presence of GAT-Mphi syngeneic to the Mphi used for in vivo priming; responses in cultures with GAT-Mphi allogeneic to the priming Mphi, whether these Mphi were syngeneic or allogeneic with respect to the responding spleen cells, were suppressed. The suppression was mediated by GAT-specific radiosensitive T cells. Thus, development of GAT-specific suppressor T cells appears to be a natural consequence of the immune response to GAT in responder as well as nonresponder mice. The implications of stimulation of genetically restricted immune helper T cells, and antigen-specific, but unrestricted, suppressor T cells after immunization with GAT-Mphi in vivo are discussed in the context of regulatory mechanisms in antibody responses.

scholarly journals Suppressor T-cell activity in responder x nonresponder (C57BL/10 x DBA/1)F(1) spleen cells responsive to l-glutamic acid(60)-L-alanine(30)-L-tyrosine (10)

1978 ◽  
Vol 148 (5) ◽  
pp. 1282-1291 ◽  
Author(s):  
CW Pierce ◽  
JA Kapp
Keyword(s):  
T Cells ◽  
Response Pattern ◽  
Cell Activity ◽  
Third Party ◽  
Helper T Cells ◽  
Spleen Cells ◽  
Suppressor T Cells ◽  
Subsequent Response

The ability of spleen cells from (responder X nonresponder)F(1) mice immunized with various GAT-Mφ, GAT-MBSA, and soluble GAT to develop IgG GAT-specific PFC responses in vitro after stimulation with responder and nonresponder parental and F(1) GAT-Mφ, was investigated. F(1) spleen cells from mice immunized with F(1) GAT-Mφ or GAT-MBSA developed secondary responses to responder and nonresponder parental and F(1) GAT- Mφ, but not to unrelated third party GAT-Mφ. Spleen cells from F(1) mice immunized with either parental GAT-Mφ developed secondary responses to F(1) GAT-Mφ and only the parental GAT-Mφ used for immunization in vivo. Soluble GAT-primed F(1) spleen cells responded to F(1) and responder parental, but not nonresponder parental, GAT-Mφ. Simultaneous immunization in vivo with the various GAT-Mφ or GAT-MBSA plus soluble GAT modulated the response pattern of these F(1) spleen cells such that they developed secondary responses only to F(1) and parental responder GAT-Mφ regardless of the response pattern observed after immunization with the various GAT-Mφ or GAT-MBSA alone. These observations demonstrate the critical importance of the physical state of the GAT used for immunization in determining the subsequent response pattern of immune F(1) spleen cells to the parental and F(1) GAT-Mφ. Further, suppressor T cells, capable of inhibiting primary responses to GAT by virgin F(1) spleen cells stimulated by nonresponder parental GAT-Mφ, were demonstrated in spleens of F(1) mice immunized with soluble GAT, but not those primed with F(1) GAT-Mφ. Because responder parental mice develop both helper and suppressor T cells after immunization with GAT-Mφ, and soluble GAT preferentially stimulates suppressor T cells whereas GAT-Mφ stimulate helper T cells in nonresponder parental mice, these observations suggest that distinct subsets of T cells exist in F(1) mice which behave phenotypically as responder and nonresponder parental T cells after immunization with soluble GAT and GAT- Mφ.

scholarly journals Mechanisms of idiotype suppression. I. In vitro generation of idiotype-specific suppressor T cells by anti-idiotype antibodies and specific antigen.

1979 ◽  
Vol 149 (6) ◽  
pp. 1371-1378 ◽  
Author(s):  
B S Kim
Keyword(s):  
T Cells ◽  
Specific Antigen ◽  
Suppressor Cells ◽  
Culture Period ◽  
Spleen Cells ◽  
Suppressor T Cells ◽  
Myeloma Protein ◽  
Specific Suppressor T Cells

Normal BALB/c spleen cells are unresponsive in vitro to the phosphorylcholine (PC) determinant in the presence of anti-idiotype antibodies specific for the TEPC-15 myeloma protein (T15) which carries an idiotypic determinant indistinguishable from that of most anti-PC antibodies in BALB/c mice. The possibility that idiotype-specific suppressor cells may be generated during the culture period was examined by coculturing the cells with untreated syngeneic spleen cells. Cells that had been preincubated with anti-T15 idiotype (anti-T15id) antibodies and a PC-containing antigen, R36a for 3 d, were capable of specifically suppressing the anti-PC response of fresh normal spleen cells, indicating that idiotype-specific suppressor cells were generated during the culture period. The presence of specific antigen also appeared to be necessary because anti-T15id antibodies and a control antigen, DNP-Lys-Ficoll, were not capable of generating such suppressor cells. Suppressor cells were induced only in the population of spleen cells nonadherent to nylon wool and the suppressive activity was abrogated by treatment with anti-Thy 1.2 serum and complement. These results indicate that anti-idiotype antibodies and specific antigen can generate idiotype-specific suppressor T cells in vitro. These in vitro results may reflect in vivo mechanisms of idiotype suppression.

scholarly journals Antigen-specific T-cell-mediated suppression. I. Induction of L-glutamic acid(60)-L-alanine(30)-L-tyrosine(10) specific suppressor T cells in vitro requires both antigen-specific T-cell-suppressor factor and antigen

1978 ◽  
Vol 147 (1) ◽  
pp. 123-136 ◽  
Author(s):  
RN Germain ◽  
J Theze ◽  
JA Kapp ◽  
B Benacerraf
Keyword(s):  
T Cells ◽  
T Cell ◽  
Sheep Erythrocyte ◽  
Suppressor Cell ◽  
Random Copolymer ◽  
Suppressor T Cells ◽  
Suppressor Factor ◽  
Specific Suppressor T Cells

A combination of in vitro and in vivo techniques were used to explore the mode of action of both crude and purified suppressive extracts specific for the random copolymer L-giutamic acid(60)-L-alanine(30)-L-tyrosine(10) (GAT- T(s)F) obtained from nonresponder DBA/1 (H-2(q)) mice. Normal DBA/1 spleen cells were incubated under modified Mishell-Dutton culture conditions for 2 days together with crude or purified GAT-T(s)F, and in the presence or absence of free GAT. These cells were then washed extensively and 3 × 10(6) viable cells transferred to syngeneic recipients, which were challenged at the same time with the immunogenic form of GAT complexed to methylated bovine serum albumin (GAT-MBSA). GAT-specific IgG plaque-forming cells (PFC) in the spleen were assayed 7 days later. In agreement with earlier in vitro studies on the action of GAT-T(s)F, it was demonstrated that under these conditions, low concentrations of GAT-T(s)F stimulated the development of cells which, aider transfer, are able to suppress the GAT PFC response to GAT-MBSA. The cells responsible for this suppression were shown to be T lymphocytes by using nylon wool-purified T cells for suppressor cell induction and by eliminating suppressive activity in cells cultured with crude GAT-T(s)F by treatment with anti-Thy 1.2 plus C before transfer. The suppressor T cells act in a specific manner failing to suppress significantly either anti-sheep erythrocyte or trinitrophenyl-ovalbumin primary PFC responses. For the induction of GAT-specific suppressor T cells in culture, a moiety bearing H- 2(K(q) or I(q)) determinants and also GAT, either bound to the crude GAT- T(s)F or added in nanogram amounts to antigen (GAT)-free purified GAT-T(s)F, were both required.

scholarly journals Suppressor T cells activated in a primary in vitro response to non-major histocompatibility alloantigens.

1982 ◽  
Vol 156 (5) ◽  
pp. 1398-1414 ◽  
Author(s):  
S Macphail ◽  
O Stutman
Keyword(s):  
Mixed Lymphocyte Reaction ◽  
Cytotoxic T Lymphocyte ◽  
Suppressor Cells ◽  
Suppressor Cell ◽  
Spleen Cells ◽  
Suppressor T Cells ◽  
Normal Spleen ◽  
In Vitro Response

Normal mouse spleen cells are not capable of mounting a primary cytotoxic T lymphocyte (Tc) response to non-H-2 alloantigens in vitro, although a good secondary H-2-restricted response is observable after in vivo immunization of the responder animals. Suppressor cells are generated in such a primary responses provided a Mls incompatibility exists between the responder and stimulator. These suppressors are not antigen specific, are Thy-1+, Lyt-1+, 2-, I-J-, and are highly radiosensitive. The suppressor cell precursors in normal spleen express the same phenotype. These suppressor cells are probably implicated in the lack of a primary Tc response in a primary mixed lymphocyte reaction across non-H-2 incompatibilities that include an Mls difference.

scholarly journals Two distinct mechanisms regulate the in vivo generation of cytotoxic T cells.

1982 ◽  
Vol 156 (3) ◽  
pp. 918-923 ◽  
Author(s):  
M S Sy ◽  
S H Lee ◽  
M Tsurufuji ◽  
K L Rock ◽  
B Benacerraf ◽  
...  
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Concanavalin A ◽  
Cytotoxic T Cells ◽  
Cytolytic T Lymphocytes ◽  
Spleen Cells ◽  
Suppressor T Cells ◽  
Con A

Treatment of responder cells with monoclonal anti-Ly-1,2 antibodies plus complement in vitro completely eliminated their ability to generate azobenzenearsonate (ABA)-specific cytolytic T lymphocytes (CTL). However, addition of the concanavalin A-stimulated supernatants of rat spleen cells (Con A-Sup) can fully reconstitute the response. Therefore, Lyt-1,2-bearing T cells are required for the generation of ABA-specific CTL, and such requirement can be replaced by factors present in the Con A- sup. Suppressor T cells (Ts), when adoptively transferred into naive recipients, will inhibit the in vivo priming of CTL. This inhibition can also be reversed by in vitro addition of Con A-Sup. furthermore, mice serving as donors of Ts also show profound unresponsiveness when primed and restimulated in vitro. In contrast to the Ts-mediated inhibition, in vitro addition of Con A-Sup was unable to abolish the unresponsiveness observed in these cultures. Thus, we identified two unresponsive states in a hapten-specific killing system that differ in their ability to be reconstituted by Con A-Sup.

scholarly journals Differential major histocompatibility complex-related activation of idiotypic suppressor T cells. Suppressor T cells cross-reactive to two distantly related lysozymes are not induced by one of them.

1980 ◽  
Vol 152 (3) ◽  
pp. 521-531 ◽  
Author(s):  
L Adorini ◽  
M A Harvey ◽  
D Rozycka-Jackson ◽  
A Miller ◽  
E E Sercarz
Keyword(s):  
T Cells ◽  
T Cell ◽  
Suppressor Cells ◽  
Suppressor Cell ◽  
Cross Reactivity ◽  
Suppressor T Cells ◽  
Cell Repertoire ◽  
Helper Cells

B10 (H-2b) mice are genetic nonresponders to hen egg-white lysozyme (HEL) and the distantly related human lysozyme (HUL). However, anti-HEL or anti-HUL primary antibody responses in vivo or in vitro can be obtained in B10 mice by immunization with the appropriate lysozyme coupled to erythrocytes. T cells able to suppress either anti-lysozyme plaque-forming cells (PFC) response are induced in B10 mice after immunization with HEL-complete Freund's adjuvant (CFA) or HUL-CFA. This cross-reactivity of HEL and HUL in the induction and the expression of suppressive activity is in marked contrast to their very low cross-reactivity at the PFC level. These results suggest that either HEL or HUL can stimulate a suppressor T cell which recognizes a particular epitope present on both lysozymes. Suppressor cells induced by HEL or HUL bear the same predominant idiotype found on the majority of anti-HEL antibodies, and on the small proportion of anti-HUL antibodies cross-reactive with HEL. B10.Q (H-2q) mice are responders in vivo to HEL-CFA, but not to HUL-CFA. In contrast to B10, HEL-CFA priming in B10.Q micr induces helper cells whereas HUL-CFA priming induces suppressor cells. These suppressor cells are cross-reactive with HEL and are fully able to suppress HEL-specific helper cells. The presence of HEL-specific suppressor cell precursors in B10.Q mice which are not activated by HEL, seems to implicate differential choice by the antigen presenting system as a basis for Ir gene control, rather than the absence of a regulatory cell type from the T cell repertoire.

scholarly journals Mechanisms of genetic resistance to Friend virus leukemia. III. Susceptibility of mitogen-responsive lymphocytes mediated by T cells.

1976 ◽  
Vol 143 (4) ◽  
pp. 728-740 ◽  
Author(s):  
V Kumar ◽  
T Caruso ◽  
M Bennett
Keyword(s):  
T Cells ◽  
B Cell ◽  
Genetic Resistance ◽  
Suppressor Cells ◽  
Suppressor Cell ◽  
M Cells ◽  
Spleen Cells ◽  
T Suppressor Cells

Friend leukemia virus (FV) suppressed the proliferative responses of spleen, lymph node, marrow, and thymus cell populations to various T- and B-cell mitogens. Cells taken from mice, e.g. BALB/c genetically susceptible to leukemogenesis in vivo were much more susceptible to suppression of mitogenesis in vitro than similar cells from genetically resistant mice, e.g., C57BL/6. Nylon wool-purified splenic T cells from BALB/c and C3H mice lost susceptibility to FV-induced suppression of mitogenesis but became suppressible by addition of 10% unfiltered spleen cell. Thus, FV mediates in vitro suppression of lymphocyte proliferation indirectly by "activating" a suppressor cell. The suppressor cell adhered to nylon wool but not to glass wool or rayon wool columns. Pretreatment of spleen cells with carbonyl iron and a magnet did not abrogate the suppressor cell function. Suppressor cells were not eliminated by treatment with rabbit antimouse immunoglobulin (7S) and complement (C). However, high concentrations of anti-Thy-1 plus C destroyed suppressor cells of the spleen; thymic suppressor cells were much more susceptible to anti-Thy-1 serum. Nude athymic mice were devoid of suppressor cells and their B-cell proliferation was relatively resistant to FV-induced suppression in vitro. The suppressor cells in the thymus (but not in the spleen) were eliminated by treatment of mice with cortisol. Thus, FV appears to mediate its suppressive effect on mitogen-responsive lymphocytes by affecting "T-suppressor cells." Spleen cells from C57BL/6 mice treated with 89Sr to destroy marrow-dependent (M) cells were much more suppressible by FV in virto than normal C57BL/6 spleen cells. However, nylon-filtered spleen cells of 89Sr-treated C57BL/6 mice were resistant to FV-induced suppression in vitro, indicating that the susceptibility of spleen cells from 89Sr-treated B6 mice is also mediated by suppressor cells. Normal B6 splenic T cells were rendered susceptible to FV-induced suppression of mitogenesis by addition of 10% spleen cells from 89Sr-treated B6 mice. Thus, M cells appear to regulate the numbers and/or functions of T-suppressor cells which in turn mediate the immunosuppressive effects of FV in vitro. Neither mitogen-responsive lymphocytes nor T-suppressor cells are genetically resistant or susceptible to FV. The genetic resistance to FV is apparently a function of M cells, both in vitro as well as in vivo.

scholarly journals Immune responses during pregnancy. Evidence of suppressor cells for splenic antibody response.

1979 ◽  
Vol 150 (4) ◽  
pp. 898-908 ◽  
Author(s):  
K Suzuki ◽  
T B Tomasi
Keyword(s):  
Antibody Response ◽  
Cell Activity ◽  
Suppressor Cells ◽  
Suppressor Cell ◽  
Adherent Cell ◽  
Spleen Cells ◽  
Normal Spleen ◽  
Pregnant Mice

The primary IgM antibody response to sheep erythrocytes in vivo as well as in vitro is markedly decreased in the spleen cells of pregnant mice, compared to age-matched female controls. Decreased antibody synthesis appears to be mediated by nonspecific suppressor cells, because the addition of pregnant spleen cells to the normal spleen cell cultures causes a significant suppression of plaque-forming-cell responses of the normal spleen cells. Suppressor cell activity was not observed in lymph nodes of pregnant mice. At least two populations of pregnant spleen cells were shown to exert a suppressor cell activity; one is T lymphocytes and the other a nylon-adherent cell present in the B-cell-enriched macrophage-depleted fraction. Pregnant spleen cells cultured in vitro were shown to secrete a soluble suppressive factor(s) into the supernatant medium.

scholarly journals Induction and mode of action of suppressor cells generated against human gamma globulin. I. An immunologic unresponsive state devoid of demonstrable suppressor cells.

1978 ◽  
Vol 148 (3) ◽  
pp. 625-638 ◽  
Author(s):  
D E Parks ◽  
M V Doyle ◽  
W O Weigle
Keyword(s):  
T Cells ◽  
B Lymphocytes ◽  
Gamma Globulin ◽  
Cell Activity ◽  
Suppressor Cells ◽  
Suppressor Cell ◽  
Spleen Cells ◽  
Suppressor T Cells ◽  
Myeloma Protein ◽  
Human Gamma Globulin

A model of unresponsiveness to human gamma-globulin (HGG) which is maintained in the absence of demonstrable suppressor cells has been described. A/J mice were tolerized with deaggregated HGG purified from a variety of sources. The spleen cells from these tolerized mice were assessed for their ability to suppress the response of normal spleen cells to HGG when transferred into lethally irradiated mice. All of the HGG preparations obtained from commercial sources as Cohn fraction II of pooled, outdated plasma induced suppressor cells to HGG, although not of equal magnitude. However, suppressor cells could not be demonstrated in the spleens of mice tolerized with deaggregated HGG purified from the plasma of a healthy individual. This inability to detect suppression was independent of the method of purification of the HGG and of the time of assessment of the putative suppressor cells after tolerization. Similarly, deaggregated HGG isolated from an IgG1 lambda-myeloma protein induced unresponsiveness to HGG but did not stimulate demonstrable suppressor cells. These data suggest that suppressor T cells are not involved in the maintenance of tolerance to this antigen, although they may play a regulatory role in the immune response to HGG. Support for this concept was obtained by assessing the duration of unresponsiveness in the T and B lymphocytes of mice tolerized with the various HGG preparations. Mice tolerized with the HGG preparations that stimulated little or no suppression were among the last to recover responsiveness. Indeed, there was no consistent correlation between the level of suppressor cell activity and the degree of unresponsiveness in either the splenic T or B lymphocytes. Thus, although certain HGG preparations may provide a tool for the generation of antigen-specific suppressor T cells, the utilization of these suppressive preparations may be inappropriate for the investigation of the mechanisms of the induction and maintenance of the unresponsive state.

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