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 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 Induction of anti-allo-class I H-2 tolerance by inactivation of CD8+ helper T cells, and reversal of tolerance through introduction of third-party helper T cells.

1990 ◽  
Vol 172 (1) ◽  
pp. 105-113 ◽  
Author(s):  
S Kitagawa ◽  
S Sato ◽  
S Hori ◽  
T Hamaoka ◽  
H Fujiwara
Keyword(s):  
T Cells ◽  
Lymphoid Cells ◽  
Third Party ◽  
Class I ◽  
Helper T Cells ◽  
Spleen Cells ◽  
Th Cells ◽  
Ctl Response

The intravenous sensitization of C57BL/6 (B6) mice with class I H-2-disparate B6-C-H-2bm1 (bm1) spleen cells resulted in the abrogation of CD8+ T cell-mediated anti-bm1 (proliferative and interleukin 2-producing) T helper (Th) cell activities. In vitro stimulation of lymphoid cells from these mice with bm1 cells, however, generated a reduced, but appreciable, anti-bm1 cytotoxic T lymphocyte (CTL) response. Moreover, the anti-bm1 CTL response, upon stimulation with [bm1 x B6-C-H-2bm12 (bm12)]F1 spleen cells, was enhanced when compared with the response induced upon stimulation with bm1 cells. These in vitro results were reflected on in vivo graft rejection responses; bm1 skin grafts engrafted in the bm1-presensitized B6 mice exhibited prolonged survival, whereas (bm1 x bm12)F1 grafts placed collateral to bm1 grafts (dual engrafted mice) inhibited the tolerance to bm1. In the B6 mice 1-2 d after rejecting the bm1 grafts, anti-bm1 Th activities remained marginal, whereas potent anti-bm1 CTL responses were found to be generated from their spleen cells. Administration in vivo of anti-CD4 antibody into bm1-presensitized, dual graft-engrafted mice prolonged bm1 graft survival and interfered with enhanced induction of anti-bm1 CTL activity. These results indicate that anti-class I alloantigen (bm1) tolerance as induced by intravenous presensitization with the relevant antigens is not ascribed to the elimination of CD8+ CTL precursors, but to the specific inactivation of CD8+ Th cells, whose function can be bypassed by activating third-party Th cells.

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 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 In vitro generation of antigen-specific helper T cells that collaborate with cytotoxic T-cell precursors.

1978 ◽  
Vol 148 (6) ◽  
pp. 1579-1591 ◽  
Author(s):  
L L Baum ◽  
L M Pilarski
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cytotoxic T Cells ◽  
Cell Activity ◽  
Helper T Cells ◽  
Helper Cell ◽  
Cytotoxic T Cell ◽  
Spleen Cells

Antigen-specific helper T cells are required in the generation of cytotoxic T cells from thymocyte precursors. We have demonstrated that these alloantigen-specific helper cells can be generated in vitro and that both the quantity and quality of the helpers appear to be superior to the help obtained from unprimed spleen cells. Optimal helper cell activity is produced at day two of culture when CBA splenic helper precursors are stimulated by irradiated allogeneic spleen cells. Helper cell precursors are antigen-specific cells which cannot be instructed to express forbidden receptor specificities and bear theta antigen on their surface. The helper effectors are radioresistant, theta-bearing, and antigen-specific cells.

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 Genetic control of immune responses in vitro. VI. Experimental conditions for the development of helper T-cell activity specific for the terpolymer L-glutamic aicd60-L-alanine30-L-tyrosine10 (GAT) in nonresponder mice.

1975 ◽  
Vol 142 (1) ◽  
pp. 50-60 ◽  
Author(s):  
J A Kapp ◽  
C W Pierce ◽  
B Benacerraf
Keyword(s):  
T Cells ◽  
Bovine Serum Albumin ◽  
Immune Responses ◽  
Specific Antibody ◽  
Cell Activity ◽  
Antibody Responses ◽  
Helper T Cells ◽  
Experimental Conditions

Mice which are genetic nonresponders to the random terpolymer of L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT) not only fail to develop GAT-specific antibody responses when stimulated with soluble GAT either in vivo or in vitro, but develop GAT-specific T cells which suppress the GAT-specific plaque-forming cell response of normal nonresponder mice stimulated with GAT complexed to methylated bovine serum albumin (MBSA).Thus, both responder and nonresponder mice have T cells which recognize GAT. However, nonresponder mice can develop GAT-specific helper T cells if immunized with GAT bound to MBSA or to macrophages. The relevance of Ir gene-controlled responses is discussed.

scholarly journals Regulatory functions of hapten-reactive helper and suppressor T lymphocytes. I. Detection and characterization of hapten-reactive suppressor T-cell activity in mice immunized with hapten-isologous protein conjugate

1977 ◽  
Vol 146 (1) ◽  
pp. 74-90 ◽  
Author(s):  
H Yamamoto ◽  
T Hamaoka ◽  
M Yoshizawa ◽  
M Kuroki ◽  
M Kitagawa
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cell ◽  
Cell Activity ◽  
Antibody Responses ◽  
Helper T Cells ◽  
Spleen Cells ◽  
Suppressor T Cells ◽  
Helper T Cell ◽  
Suppressor T Cell

Helper and suppressor T-cell activities were detected simultaneously in the spleen cells of mice immunized with para-azobenzoate (PAB)-mouse gammaglobulin (MGG). Dinitrophenyl (DNP)-specific B cells were raised by immunization with DNP-keyhole limpet hemocyanin (KLH) and used as the indicator B-cell population. The helper and suppressor T-cell activities were determined after adoptively transferring spleen cells from PAB-MGG- primed donors and DNP-KLH-primed donors into X-irradiated recipients. Stimulation of these recipients with DNP-MGG-PAB detected helper T-cell activity, which was measured in terms of increased anti-DNP antibody responses of DNP-KLH-primed cells over these responses in the presence of unprimed cells. On the other hand, when DNP-KLH-primed cells were stimulated with DNP-KLH-PAB in the presence of PAB-MGG-primed cells, anti-DNP antibody responses were substantially lower than in unprimed normal cells. This suppressor cell population was (a) hapten-reactive, (b) present in B-cell-depleted spleen cells, (c) Thy-1 positive, (d) detectable earlier than the helper T-cell activities after priming (e) more radiosensitive than helper cells, and (f) found in the spleen but not the lymph nodes in contrast to helper T cells. These data indicate that these suppressor T cells are distinct from the helper T cells. PAB-reactive T cells clearly suppressed the antibody response by inhibiting KLH-reactive helper T-cell functions. The hapten-reactive T-lymphocyte system described here should be useful for analyzing and manipulating the immune response and for studying regulatory interactions of helper and suppressor T cells in the induction of antibody responses.

scholarly journals Regulatory functions of hapten-reactive helper and suppressor T lymphocytes. II. Selective inactivation of hapten-reactive suppressor T cells by hapten-nonimmunogenic copolymers of D-amino acids, and its application to the study of suppressor T-cell effect on helper T-cell development

1977 ◽  
Vol 146 (1) ◽  
pp. 91-106 ◽  
Author(s):  
T Hamaoka ◽  
M Yoshizawa ◽  
H Yamamoto ◽  
M Kuroki ◽  
M Kitagawa
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
T Cell Development ◽  
Cell Activity ◽  
Helper T Cells ◽  
Suppressor T Cells ◽  
Helper T Cell ◽  
Suppressor T Cell ◽  
Suppressor T Lymphocytes

An experimental condition was established in vivo for selectively eliminating hapten-reactive suppressor T-cell activity generated in mice primed with a para-azobenzoate (PAB)-mouse gamma globulin (MGG)-conjugate and treated with PAB-nonimmunogenic copolymer of D-amino acids (D- glutamic acid and D-lysine; D-GL). The elimination of suppressor T-cell activity with PAB-D-GL treatment from the mixed populations of hapten- reactive suppressor and helper T cells substantially increased apparent helper T-cell activity. Moreover, the inhibition of PAB-reactive suppressor T-cell generation by the pretreatment with PAB-D-GL before the PAB-MGG-priming increased the development of PAB-reactive helper T-cell activity. The analysis of hapten-specificity of helper T cells revealed that the reactivity of helper cells developed in the absence of suppressor T cells was more specific for primed PAB-determinants and their cross-reactivities to structurally related determinants such as meta-azobenzoate (MAB) significantly decreased, as compared with the helper T-cell population developed in the presence of suppressor T lymphocytes. In addition, those helper T cells generated in the absence of suppressor T cells were highly susceptible to tolerogenesis by PAB-D- GL. Similarly, the elimination of suppressor T lymphocytes also enhanced helper T-cell activity in a polyclonal fashion in the T-T cell interactions between benzylpenicilloyl (BPO)-reactive T cells and PAB- reactive T cells after immunization of mice with BPO-MGG-PAB. Thus inhibition of BPO-reactive suppressor T-cell development by the BPO-v-GL- pretreatment resulted in augmented generation of PAB-reactive helper T cells with higher susceptibility of tolerogenesis to PAB-D-GL. Thus, these results support the notion that suppressor T cells eventually suppress helper T-cell activity and indicate that the function of suppressor T cells related to helper T-cell development is to inhibit the increase in the specificity and apparent affinity of helper T cells in the primary immune response. The hapten-reactive suppressor and helper T lymphocytes are considered as a model system of T cells that regulate the immune response, and the potential applicability of this system to manipulating various T cell-mediated immune responses is discussed in this context.

scholarly journals IMMUNOLOGIC REACTIONS TO HAPTENS ON AUTOLOGOUS CARRIERS

1973 ◽  
Vol 137 (2) ◽  
pp. 411-423 ◽  
Author(s):  
John W. Moorhead ◽  
Curla S. Walters ◽  
Henry N. Claman
Keyword(s):  
T Cells ◽  
B Cells ◽  
Aminocaproic Acid ◽  
Single Amino Acid ◽  
Secondary Response ◽  
Spleen Cells ◽  
Activated T Cells ◽  
Thymus Cells

Both thymus-derived (T) and bone marrow-derived (B) lymphocytes participate in the response to a hapten 4-hydroxy-3-iodo-5-nitrophenylacetic acid (NIP), coupled to a nonimmunogenic isologous carrier, mouse gamma globulin (MGG). Spleen cells from mice immunized with NIP-MGG show increased DNA synthesis in vitro when cultured with NIP-MGG. The participation of and requirement for T cells in the response was demonstrated by treating the spleen cells with anti-θ serum. This treatment resulted in a 77% inhibition of the antigen response. Furthermore, adoptively transferred normal thymus cells could be specifically "activated" by NIP-MGG in vivo and they responded secondarily to the antigen in vitro. The active participation of B cells in the secondary response was demonstrated by passing the immune spleen cells through a column coated with polyvalent anti-MGG serum. Column filtration reduced the number of NIP-specific plaque-forming cells and NIP-specific rosette-forming cells (both functions of B cells) and produced a 47% inhibition of the NIP-MGG response. The ability of the cells to respond to phytohemagglutinin (PHA) was not affected by column filtration showing that T cells were not being selectively removed. The participation of B cells in the in vitro NIP-MGG response was also shown by treatment of the spleen cells with antiserum specific for MGG and MGG determinants. B cells were removed by treatment with anti-IgM or polyvalent anti-MGG serum plus complement, resulting in a respective 46 and 49% inhibition of the response to NIP-MGG. (Treatment with anti-IgM serum had no effect on T cells.) The contribution of the hapten NIP to stimulation of T cells was investigated using NIP-MGG-activated thymus cells. These activated T cells responded in vitro very well to the NIP-MGG complex but not to the MGG carrier alone demonstrating the requirement of the hapten for T cell stimulation. The response was also partially inhibited (41%) by incubating the activated cells with NIP coupled to a single amino acid (epsilon-aminocaproic acid) before addition of NIP-MGG. These results demonstrated that T cells recognize the hapten NIP when it is coupled to the isologous carrier MGG.

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