scholarly journals Hapten-specific T cell responses to 4-hydroxy-3-nitrophenyl acetyl. III. Interaction of effector suppressor T cells is restricted by H-2 and Igh-V genes.

1980 ◽  
Vol 151 (6) ◽  
pp. 1413-1423 ◽  
Author(s):  
J Z Weinberger ◽  
B Benacerraf ◽  
M E Dorf
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Population ◽  
Suppressor Cells ◽  
Delayed Type Hypersensitivity ◽  
Suppressor T Cells ◽  
Cellular Models ◽  
Cell Responses ◽  
Histocompatibility Complex ◽  
V Genes

4-Hydroxy-3-nitrophenyl acetyl (NP)-derivatized syngeneic spleen cells administered intravenously induced a population of suppressor T cells that could suppress mice previously primed to NP. The effect was demonstrable when the suppressor cells were transferred to NP-primed mice on the day of challenge for delayed-type hypersensitivity (DTH) responses. In contrast to the suppressor T cell population, which abrogates 5-iodo derivative of NP (NIP)-specific DTH responses when administered before antigen priming, the effector-phase suppressors did not efficiently suppress NIP-specific DTH responses, and were not lysed by treatment with antiidiotype plus complement. Adoptive transfer experiments between major histocompatibility complex and allotype congenic strains of mice allowed demonstration of both Igh-V and I-A restrictions in the transfer of this cell population. The implications of these data in terms of network theories and proposed cellular models for negative immunoregulation were discussed.

scholarly journals Presence on idiotype-specific suppressor T cells of receptors that interact with molecules bearing the idiotype.

1977 ◽  
Vol 145 (6) ◽  
pp. 1559-1566 ◽  
Author(s):  
F L Owen ◽  
S T Ju ◽  
A Nisonoff
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Population ◽  
Suppressor Cells ◽  
Suppressive Activity ◽  
Suppressor T Cells ◽  
Suppressor T Cell ◽  
Fab Fragments ◽  
Large Numbers ◽  
Specific Suppressor T Cells

All A/J mice produce anti-p-azophenylarsonate (anti-Ar) antibodies, some of which share a cross-reactive idiotype. The idiotype can be suppressed by treatment with anti-idiotypic antiserum before immunization, although normal concentrations of anti-Ar antibodies are synthesized. We have previously reported that such suppressed mice, if hyperimmunized and then allowed to rest, contain up to 10% of splenic T cells which form rosettes with autologous RBC coated with Fab fragments of anti-Ar antibodies bearing the idiotype. Our present results indicate that the rosette-forming T cells include the idiotype-specific suppressor T-cell population. The suppressive activity is largely depleted by removal of the rosette-forming lymphocytes, and the rosettes themselves are highly suppressive. The data do not establish whether all of the idiotype-specific rosette-forming cells are suppressor cells. The system may provide a source of large numbers of suppressor cells for further study, and facilitate investigation of the mechanism of generation of idiotype-specific suppressor cells.

scholarly journals Hapten-specific responses to the phenyltrimethylamino hapten. III. Mice whose delayed-type hypersensitivity responses cannot be abrogated by the presence of anti-idiotypic suppressor T cells lack a critical modulatory T cell function.

1982 ◽  
Vol 155 (6) ◽  
pp. 1810-1822 ◽  
Author(s):  
S Jayaraman ◽  
C J Bellone
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Population ◽  
Cell Function ◽  
Suppressor Cell ◽  
Delayed Type Hypersensitivity ◽  
Loss Of Function ◽  
Suppressor T Cells ◽  
T Cell Function ◽  
Cyclophosphamide Treatment

A single intraperitoneal injection of the monovalent synthetic antigen, tyrosinated trimethylaminoaniline [tyr(TMA)] in Freund's complete adjuvant induces an antiidiotypic second-order T suppressor (Ts2) cell population 6 wk later. This population was able to suppress TMA-specific delayed-type hypersensitivity (DTH) responses when adoptively transferred into normal syngeneic recipients. However, they failed to function intrinsically. The inability of the Ts2 to function intrinsically was not caused by compensating idiotype-negative T cells that mediate DTH. Rather, this paradoxical observation was found to be caused by the absence or loss of function of a critical modulatory T cell population in the suppressor cell-bearing mice. This cell is functionally active in normal mice immunized for DTH responses and is sensitive to cyclophosphamide treatment. In addition, this cell type bears idiotype on its surface and is Thy-1+ and Lyt-1-,2+. It was demonstrated that by adoptively transferring the activated modulatory T cells from normal mice into tyr(TMA)-immune recipients, it was possible to observe suppressor cell function intrinsically. The potential importance of modulatory T cell function in the regulation of antibody and DTH responses is discussed.

scholarly journals An antigen-specific signal is required for the activation of second-order suppressor T cells in the regulation of delayed-type hypersensitivity to 2,4,6-trinitrobenzene sulfonic acid.

1983 ◽  
Vol 158 (3) ◽  
pp. 932-945 ◽  
Author(s):  
M Tsurufuji ◽  
B Benacerraf ◽  
M S Sy
Keyword(s):  
T Cells ◽  
Sulfonic Acid ◽  
Suppressor Cells ◽  
Delayed Type Hypersensitivity ◽  
Trinitrobenzene Sulfonic Acid ◽  
Spleen Cells ◽  
Suppressor T Cells ◽  
Histocompatibility Complex

Suppressor T cells (Ts-1) induced with trinitrophenyl (TNP)-conjugated syngeneic spleen cells (TNP-SC) can be enriched on antigen-coated plates and are afferent suppressors. In addition, these suppressor cells produced soluble suppressor factors (TsF) that were active in vivo. Therefore, the Ts-1 cells in the TNP system are very similar to the Ts-1 cells in other systems we have studied earlier. Further characterization of these TsF-1 revealed that TsF-1 obtained from TNP-SC-induced Ts-1 is major histocompatibility complex restricted in its activity. Injection of TNP-specific TsF-1 into naive mice did not induce Ts-2 unless additional corresponding antigen was provided. Moreover, the Ts-2 cells induced by administration of both TsF-1 and trinitrobenzene sulfonic acid were antigen specific rather than antiidiotypic.

scholarly journals Endogenous dendritic cells mediate the effects of intravenously injected therapeutic immunosuppressive dendritic cells in transplantation

Blood ◽  
2010 ◽  
Vol 116 (15) ◽  
pp. 2694-2705 ◽  
Author(s):  
Sherrie J. Divito ◽  
Zhiliang Wang ◽  
William J. Shufesky ◽  
Quan Liu ◽  
Olga A. Tkacheva ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Indirect Pathway ◽  
Allograft Survival ◽  
Complex Molecules ◽  
Cell Responses ◽  
Histocompatibility Complex

Abstract The prevailing idea regarding the mechanism(s) by which therapeutic immunosuppressive dendritic cells (DCs) restrain alloimmunity is based on the concept that they interact directly with antidonor T cells, inducing anergy, deletion, and/or regulation. However, this idea has not been tested in vivo. Using prototypic in vitro–generated maturation-resistant (MR) DCs, we demonstrate that once MR-DCs carrying donor antigen (Ag) are administered intravenously, they decrease the direct and indirect pathway T-cell responses and prolong heart allograft survival but fail to directly regulate T cells in vivo. Rather, injected MR-DCs are short-lived and reprocessed by recipient DCs for presentation to indirect pathway CD4+ T cells, resulting in abortive activation and deletion without detrimental effect on the number of indirect CD4+ FoxP3+ T cells, thus increasing the regulatory to effector T cell relative percentage. The effect on the antidonor response was independent of the method used to generate therapeutic DCs or their viability; and in accordance with the idea that recipient Ag-presenting cells mediate the effects of therapeutic DCs in transplantation, prolongation of allograft survival was achieved using donor apoptotic MR-DCs or those lacking surface major histocompatibility complex molecules. We therefore conclude that therapeutic DCs function as Ag-transporting cells rather than Ag-presenting cells to prolong allograft survival.

scholarly journals Antigen- and receptor-driven regulatory mechanisms. II. Induction of suppressor T cells with idiotype-coupled syngeneic spleen cells.

1979 ◽  
Vol 150 (5) ◽  
pp. 1229-1240 ◽  
Author(s):  
M S Sy ◽  
B A Bach ◽  
A Brown ◽  
A Nisonoff ◽  
B Benacerraf ◽  
...  
Keyword(s):  
T Cells ◽  
Heavy Chain ◽  
Suppressor Cells ◽  
Significant Inhibition ◽  
Regulatory Mechanisms ◽  
Delayed Type Hypersensitivity ◽  
Spleen Cells ◽  
Suppressor T Cells ◽  
Specific Manner ◽  
Coupled Cells

Anti-p-azobenzenearsonate (ABA) antibodies, coupled covalently to normal syngeneic spleen cells and then given intravenously to normal animals, were found to be potent tolerogens for delayed-type hypersensitivity (DTH) to ABA. The ability of the antibody-coupled cells to induce tolerance was determined to be a result of the cross-reactive idiotype (CRI+) fraction of the antibodies, because anti-ABA antibodies lacking the CRI+ components when coupled to spleen cells were unable to cause any significant inhibition. Furthermore, genetic analysis revealed that the ability of CRI-coupled cells to inhibit ABA-specific DTH is linked to Igh-1 heavy chain allotype, in as much animals which possess heavy chain allotypes similar to that of A/J were sensitive to this inhibition. Adoptive transfer experiments provided evidence that CRI-coupled cells induce suppressor cells, and spleen cells or thymocytes from animals received CRI-coupled cells were able to transfer suppression to naive recipients. In addition, treatment with anti-Thy1.2 serum plus complement completely abrogated their ability to transfer suppression. Thus, this active suppression is a T-cell-dependent phenomenon. In investigating the specificity of these suppressor T cells, it was found that they functioned in an antigen-specific manner and were unable to suppress the development of DTH to an unrelated hapten 2,4-dinitro-1-fluorobenzene.

scholarly journals Regression and inhibition of sarcoma growth by interference with a radiosensitive T-cell population.

1978 ◽  
Vol 148 (3) ◽  
pp. 799-804 ◽  
Author(s):  
K E Hellström ◽  
I Hellström ◽  
J A Kant ◽  
J D Tamerius
Keyword(s):  
T Cells ◽  
T Cell ◽  
Tumor Growth ◽  
Cell Population ◽  
Whole Body ◽  
Spleen Cells ◽  
Suppressor T Cells ◽  
Irradiation Irradiation

BALB/c mice were inoculated subcutaneously with 10(6) cells from either of two syngeneic sarcomas 1315 and 1425. 6--8 days later, the mice were randomized into groups which were left untreated or given 400 rads of whole body irradiation. Irradiation significantly retarded the growth of both sarcomas, and complete regressions were seen of approximately equal to 30% of the small, established 1315 tumors. The anti-tumor effect of irradiation was abolished if the irradiated mice were inoculated with a T-cell-enriched (but not with a T-cell deprived) suspension of syngeneic spleen cells, suggesting that the irradiation inhibited tumor growth by affecting a radiosensitive population of host suppressor T cells.

scholarly journals Antigen- and receptor-driven regulatory mechanisms. IV. Idiotype-bearing I-J+ suppressor T cell factors induce second-order suppressor T cells which express anti-idiotypic receptors.

1980 ◽  
Vol 151 (5) ◽  
pp. 1183-1195 ◽  
Author(s):  
M S Sy ◽  
M H Dietz ◽  
R N Germain ◽  
B Benacerraf ◽  
M I Greene
Keyword(s):  
T Cells ◽  
T Cell ◽  
Specific Binding ◽  
Suppressor Cells ◽  
T Cell Subsets ◽  
Regulatory Pathway ◽  
Spleen Cells ◽  
Suppressor T Cells ◽  
Suppressor Factor ◽  
Ig Heavy Chain

Administration of azobenzenearsonate (ABA)-coupled syngeneic spleen cells intravenously to A/J mice leads to the generation of suppressor T cells (Ts1) which exhibit specific binding to ABA-bovine serum albumin (BSA)-coated dishes. These Ts1 share idiotypic determinants with the major cross-reactive idiotype (CRI) of the anti-ABA antibodies of A/J mice, and also produce a soluble suppressor factor (TsF) bearing CRI and I-J subregion-coded determinants. Injection of this TsF into naive A/J mice elicits a second set of specific suppressor cells (Ts2) which are not lysed by anti-CRI antibody plus C, and which do not bind to ABA-BSA-coated dishes. However, in contrast with Ts1, these Ts2 do bind to plates bearing CRI+ anti-ABA immunoglobulin. Thus, Ts2 exhibit anti-idiotypic specificity. These data indicate that antigen elicits the production of a soluble T cell product bearing both variable portion of the Ig heavy chain (VH) and I-J subregion-coded determinants which serves to communicate between T cell subsets to establish an idiotype-anti-idiotype regulatory pathway.

scholarly journals Tolerance to parenchymal self. Regulatory role of major histocompatibility complex-restricted, OX8+ suppressor T cells specific for autologous renal tubular antigen in experimental interstitial nephritis.

1985 ◽  
Vol 162 (6) ◽  
pp. 1892-1903 ◽  
Author(s):  
C J Kelly ◽  
W K Silvers ◽  
E G Neilson
Keyword(s):  
T Cells ◽  
Interstitial Nephritis ◽  
Clonal Expansion ◽  
Delayed Type Hypersensitivity ◽  
Cell Mediated Immunity ◽  
Suppressor T Cells ◽  
Rat Strains ◽  
Histocompatibility Complex ◽  
Renal Tubular

BN rats develop interstitial nephritis after immunization with rabbit, but not rat renal tubular antigen. Using RT1n rat strains that differentially express tubular antigen, we investigated the unresponsiveness of BN rats to BN tubular antigen (BN-TBM) using delayed-type hypersensitivity (DTH) responses to BN-TBM as a measure of cell-mediated immunity. Our results indicate that rat strains expressing tubular antigen respond to immunization with BN-TBM with the clonal expansion of antigen-specific, cyclophosphamide-sensitive, OX8+, MHC-restricted suppressor T cells. Such suppression appears to be relevant to the maintenance of tolerance to parenchymal self, since chronic cyclophosphamide therapy abrogates suppression and results in significant interstitial nephritis.

scholarly journals Immune suppression in vivo with antigen-modified syngeneic cells. I. T-cell-mediated suppression to the terpolymer poly-(Glu, Lys, Phe)n.

1978 ◽  
Vol 148 (6) ◽  
pp. 1539-1549 ◽  
Author(s):  
N K Cheung ◽  
D H Scherr ◽  
K M Heghinian ◽  
B Benacerraf ◽  
M E Dorf
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Suppression ◽  
Cell Response ◽  
Gamma Globulin ◽  
Suppressor Cells ◽  
Spleen Cells ◽  
Suppressor T Cells ◽  
Specific Suppressor T Cells

The palmitoyl derivative of the linear polypeptide of poly-(L-Glu-L-Lys-L-Phe)n (GLphi) can be coupled to spleen cells directly. The intravenous administration of 2 X 10(5)--3 X 10(7) GLphi-coupled syngeneic spleen cells induces GL-phi-specific suppressor T cells in C57BL/6 nonresponder mice. The suppression is antigen specific and can be detected by the inhibition of the primary GLphi plaque-forming cell response to challenge with GLphi-fowl gamma globulin. The number of inducer cells required for suppression carry less than 0.1 microgram of antigen. Spleen cells from tolerized mice can transfer suppression to normal syngeneic recipients. The suppression is cyclophosphamide sensitive and the suppressor cells bear the Thy 1.2 marker. This method of inducing antigen-specific suppressor cells may be generally applicable to other antigen systems.

scholarly journals CD4 memory T cells survive and proliferate but fail to differentiate in the absence of CD40

2006 ◽  
Vol 203 (4) ◽  
pp. 897-906 ◽  
Author(s):  
Megan MacLeod ◽  
Mark J. Kwakkenbos ◽  
Alison Crawford ◽  
Sheila Brown ◽  
Brigitta Stockinger ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Memory T Cells ◽  
Cell Receptor ◽  
Memory Cells ◽  
Cell Stage ◽  
Effector Cells ◽  
Cell Responses ◽  
Histocompatibility Complex ◽  
Specific Memory

Secondary T cell responses are enhanced because of an expansion in numbers of antigen-specific (memory) cells. Using major histocompatibility complex class II tetramers we have tracked peptide-specific endogenous (non–T cell receptor transgenic) CD4 memory T cells in normal and in costimulation-deficient mice. CD4 memory T cells were detectable after immunization for more than 200 days, although decay was apparent. Memory cells generated in CD40 knockout mice by immunization with peptide-pulsed wild-type dendritic cells survived in the absence of CD40 and proliferated when boosted with peptide (plus adjuvant) in a CD40-independent fashion. However, differentiation of the memory cells into cytokine-producing effector cells did not occur in the absence of CD40. The data indicate that memory cells can be generated without passing through the effector cell stage.

Sign in / Sign up

Export Citation Format

Share Document