scholarly journals Immunoregulatory T cell circuits in man. Alloantigen-primed inducer T cells activate alloantigen-specific suppressor T cells in the absence of the initial antigenic stimulus.

1983 ◽  
Vol 158 (1) ◽  
pp. 159-173 ◽  
Author(s):  
N K Damle ◽  
E G Engleman
Keyword(s):  
T Cells ◽  
T Cell ◽  
Human Peripheral Blood ◽  
Cytotoxic T Cells ◽  
Suppressor Cells ◽  
Suppressive Effect ◽  
Third Party ◽  
T Cell Subsets ◽  
Suppressor T Cells ◽  
Specific Suppressor T Cells

Although alloantigen-specific suppressor T cells are generated in MLR, the cellular signals that lead to activation of suppressor T cells as opposed to cytotoxic T cells are unknown. The current study was undertaken to characterize interactions among T cell subsets involved in the generation of suppressor T cells in MLR. Human peripheral blood Leu-2+ (suppressor/cytotoxic) and Leu-3+ (helper/inducer) T cell subsets were activated with allogeneic non-T cells and then examined for their inductive effects on fresh autologous T cells. Fresh Leu-2+ cells proliferated in response to alloantigen-primed Leu-3+ cells and subsequently suppressed the response of fresh autologous Leu-3+ cells to the original, but not third party, allogeneic stimulator non-T cells. Moreover, only Leu-2+ cells that lacked the 9.3 marker, an antigen present on the majority of T cells including precursors of cytotoxic T cells, differentiated into suppressor cells. The alloantigen-specific suppressive effect of Leu-2+,9.3-cells was not mediated by cytolysis of allogeneic stimulator cells, nor could it be explained by alteration of MLR kinetics. Suppression was observed only when activated Leu-2+ cells were added to fresh MLRs within 24 h of initiation of cultures, suggesting that these cells block an early phase of the activation of Leu-3+ cells in MLR. These results indicate that alloantigen-primed inducer T cells can activate alloantigen-specific suppressor T cells in the absence of allogeneic stimulator 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 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 Quantitative studies on T cell diversity. II. Determination of the frequencies and Lyt phenotypes of two types of precursor cells for alloreactive cytotoxic T cells in polyclonally and specifically activated splenic T cells.

1981 ◽  
Vol 153 (4) ◽  
pp. 857-870 ◽  
Author(s):  
J Goronzy ◽  
U Schaefer ◽  
K Eichmann ◽  
M M Simon
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cytotoxic T Cells ◽  
Suppressor Cells ◽  
T Cell Subsets ◽  
Con A ◽  
Activated T Cells ◽  
Cell Diversity ◽  
Lymphocyte Populations ◽  
Limiting Dilution

Two different limiting dilution systems have been applied to compare precursor frequencies of alloreactive cytotoxic T cells (CTL-P) in the polyclonally and specifically activated lymphocyte populations and in selected Lyt T cell subsets. Both systems make use of T cell growth factor for T cell expansion but differ with respect to the activation step in that lymphocytes are either activated directly with allogenetic stimulator cells or are sensitized polyclonally with concanavalin A (Con A) in bulk culture before their expansion under limiting dilution conditions. In polyclonally activated C57BL/6 lymphocyte populations, two types of CTL-P specific for H-2d alloantigens could be identified: a frequent set with a frequency of 1/100-1/300, and a rare set with a frequency of 1/2,000-1/8,000. In contrast, only a single CTL-P set was found in specifically activated populations with a frequency similar to that of the frequent CTL-P found on Con A blasts. In Con A blasts, the frequent at higher cell concentrations by suppressor T cells, whereas rare CTL-P were insensitive to this suppressive mechanism. Whereas in specifically activated T cells, the predominant CTL-P phenotype was Lyt-123, the predominant Lyt phenotypes for the frequent and the rare CTL-P found in Con A blasts were Lyt-123 and Lyt-123, respectively, which suggests that they represent primary and secondary CTL-P, respectively. The results are discussed with respect to previous reports on the involvement of Lyt T cell subsets in the generation of cytotoxic responses and their regulation by T suppressor cells.

scholarly journals Mechanisms of idiotype suppression. IV. Functional neutralization in mixtures of idiotype-specific suppressor and hapten-specific suppressor T cells.

1981 ◽  
Vol 154 (3) ◽  
pp. 809-820 ◽  
Author(s):  
B S Kim ◽  
J A Greenberg
Keyword(s):  
T Cells ◽  
T Cell ◽  
Suppressor Cells ◽  
Suppressor Cell ◽  
Cell Types ◽  
Spleen Cells ◽  
Suppressor T Cells ◽  
Normal Spleen ◽  
Specific Receptors ◽  
Specific Suppressor T Cells

Specific tolerance to phosphorylcholine (PC) can be induced in BALB/c mice by neonatal injection with either pneumococcal C-polysaccharide (PnC) or anti-TEPC 15 idiotype (T15Id) antibody specific for the major idiotype (Id) of anti-PC antibody. Spleen cells from these tolerant mice exhibited T cell-mediated active suppression of anti-PC response when they were co-cultured with normal spleen cells. Suppressor cells from the PnC-injected mice appeared to bear either Lyt-1 or Lyt-2 antigens, whereas suppressor cells from anti-Id-treated mice expressed Lyt-2 antigens. Analyses of the specific receptors of these suppressor T cells, based on either adherence to PC and T15-coated petri dishes or cytolysis by rabbit anti-T15Id and monoclonal IgM anti-PC antibody with complement, revealed that receptors of PnC-induced suppressor T cells recognize PC, whereas receptors of anti-Id-induced suppressor T cells react with the T15Id. The possible interaction of the two different types of suppressor T cells was examined by co-culturing normal spleen cells with mixtures of the different suppressor cell types in various cell ratios in the presence of the T-independent PC-antigen, R36a. A brief incubation of anti-Id-induced, T15Id-specific suppressor T cells with PnC-induced, hapten-specific, and T15Id-bearing suppressor T cells resulted in complete cancellation of their suppressor function. These results suggest that idiotype network regulation may also occur among suppressor T cell population.

scholarly journals Tubular antigen-derivatized cells induce a disease-protective, antigen-specific, and idiotype-specific suppressor T cell network restricted by I-J and Igh-V in mice with experimental interstitial nephritis.

1985 ◽  
Vol 162 (1) ◽  
pp. 215-230 ◽  
Author(s):  
E G Neilson ◽  
E McCafferty ◽  
R Mann ◽  
L Michaud ◽  
M Clayman
Keyword(s):  
T Cells ◽  
T Cell ◽  
Interstitial Nephritis ◽  
Protective Antigen ◽  
Suppressor Cells ◽  
Donor Cell ◽  
Suppressor Cell ◽  
Suppressive Effect ◽  
T Cell Response ◽  
Suppressor T Cells

The nephritogenic effector T cell response producing interstitial nephritis in mice can be largely inhibited by the adoptive transfer of suppressor T cells before or after the induction of disease. These suppressor T cells are harvested from donor mice primed with tubular antigen-derivatized syngeneic lymphocytes, and two subsets of suppressor cells can be characterized within this donor cell population. The first suppressor cell in this network is an L3T4+, I-J+, RE-Id+ cell (Ts-1). Ts-1 cells are antigen-binding suppressor cells that inhibit afferent phase immune responses and, in the presence of tubular antigen, specifically induce Lyt-2+, I-J+ cells (Ts-2) that are antiidiotypic (RE-Id-binding) suppressors. The Ts-2 cell is functionally restricted in its suppressive effect by I-J and Igh-V gene products, and acts on the effector limb of the cell-mediated anti-tubular basement membrane immune response. These studies provide an experimental basis for further efforts to use immunoregulatory modulation in the control of autoimmune renal disease.

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.

CD3+CD4low and CD3+CD8low are induced by HLA-G: novel human peripheral blood suppressor T-cell subsets involved in transplant acceptance

Blood ◽  
2007 ◽  
Vol 110 (12) ◽  
pp. 3936-3948 ◽  
Author(s):  
Abderrahim Naji ◽  
Solene Le Rond ◽  
Antoine Durrbach ◽  
Irene Krawice-Radanne ◽  
Caroline Creput ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Peripheral Blood ◽  
Human Peripheral Blood ◽  
Plasma Concentrations ◽  
Suppressor Cells ◽  
Peripheral Tolerance ◽  
T Cell Subsets ◽  
Hla Dr ◽  
Antigen Presenting

Abstract HLA-G is a tolerogenic molecule whose detection in sera and within allografted tissues is associated with better graft acceptance. HLA-G mediates T-cell differentiation into suppressor cells, which are thought to promote tolerance. Here, we investigated such T cells phenotypically and functionally and assessed their clinical relevance in the peripheral blood of patients who have undergone transplantation. Our results demonstrate that HLA-G expressed by antigen-presenting cells or present as soluble protein down-regulates the expression of CD4 and CD8 on allostimulated T cells at both transcriptional and posttranslational levels. These CD3+CD4low and CD3+CD8low T-cell subsets are characterized by an increased proportion of cells expressing CD45RA and HLA-DR, and a decreased number of cells expressing CD62L. In addition, these HLA-G–induced CD3+CD4low and CD3+CD8low subpopulations are Foxp3-negative suppressor T cells whose function involves IL-10. Biologic relevance came from analysis of patients who underwent transplantation, with high HLA-G plasma concentrations associated with better graft survival. Peripheral blood from these patients contains increased levels of IL-10 concomitantly to an enhanced representation of CD3+CD4low and CD3+CD8low T cells compared with HLA-G–negative patients who underwent transplantation and healthy individuals. These data define novel immunosuppressive subpopulations of peripheral blood T cells induced by HLA-G with potent implications in peripheral tolerance.

scholarly journals Genetic control of specific immune suppression. IV. Responsiveness to the random copolymer L-glutamic acid(50)-L-tyrosine(50) induced in BALB/c mice by cyclophosphamide

1976 ◽  
Vol 144 (1) ◽  
pp. 277-281 ◽  
Author(s):  
P Debre ◽  
C Waltenbaugh ◽  
ME Dorf ◽  
B Benacerraf
Keyword(s):  
T Cells ◽  
T Cell ◽  
Antibody Response ◽  
Glutamic Acid ◽  
Cell Activity ◽  
Suppressor Cells ◽  
Suppressor T Cells ◽  
Helper Activity ◽  
Specific Suppressor T Cells ◽  
Stimulation Of

Previous reports from our laboratory have demonstrated the stimulation of specific suppressor T cells in genetic nonresponder mice after immunization with the terpolymer of L- glutamic acid, L-alanine, and L-tyrosine (GAT) (1,2) and with the copolymer of L-glutamic acid and L-tyrosine (GT) (3-5). These findings raise two important questions: (a) do the specific suppressor T cells inhibit an antibody response which would otherwise develop in nonresponder mice; and, (b) can specific helper T cells inhibit an antibody response which would otherwise develop in nonresponder mice; and, (b) can specific helper T-cell activity be detected in these animals. Responsiveness appears to be completely dominant over suppression in (responder x suppressor)F(1) hybrids, therefore, we have been unable to detect suppressor cells in these hybrids after conventional immunization with GAT (2). However , using special conditions of antigen administration, GAT helper activity could be demonstrated in nonresponder DBA/1 (suppressor) mice. Thus, GAT-specific helper activity was not detected in these nonresponder animals after immunization with GAT irrespective of the adjuvant used, but could be stimulated by macrophage-bound GAT or by GAT complexed with methylated bovine serum albumin GAT-MBSA (6). In the current report we have taken advantage of the fact that suppressor T-cell activity is more sensitive to cyclophosphamide treatment than T-cell helper activity (7) to demonstrate the presence of GT-specific helper activity in nonresponder BALB/c mice. We describe: (a) the dose of cyclophosphamide and conditions of treatment which inhibits the well-documented stimulation of specific suppressor T cells in BALB/c mice injected with GT previous to immunization with GT-MBSA, and (b) the ability of cyclophosphamide to permit the development of primary PFC responses to GT in these nonresponder mice. These cyclophosphamide-induced responses are not characterized by the high levels of antibody detected in genetic responder animals.

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.

6 Murine T cell subsets and interleukins: Relationships between cytotoxic T cells, helper T cells and accessory cells

1982 ◽  
Vol 11 (3) ◽  
pp. 607-630
Author(s):  
Hermann Wagner ◽  
Martin Kronke ◽  
Werner Solbach ◽  
Peter Scheurich ◽  
Martin Röllinghoff ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cytotoxic T Cells ◽  
T Cell Subsets ◽  
Helper T Cells ◽  
Accessory Cells
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