scholarly journals Antigen- and receptor-driven regulatory mechanisms. VII. H-2-restricted anti-idiotypic suppressor factor from efferent suppressor T cells.

1981 ◽  
Vol 153 (2) ◽  
pp. 450-463 ◽  
Author(s):  
M H Dietz ◽  
M S Sy ◽  
B Benacerraf ◽  
A Nisonoff ◽  
M I Greene ◽  
...  
Keyword(s):  
T Cells ◽  
Specific Binding ◽  
Cell Activity ◽  
Suppressor Cell ◽  
Delayed Type Hypersensitivity ◽  
Suppressor T Cells ◽  
Suppressor Factor ◽  
Restricted Activity ◽  
Efferent Suppression ◽  
Delayed Type Hypersensitivity Response

Azobenzenearsonate (ABA)-specific T cell-derived suppressor factor (TsF1) from A/J mice was used to induced second-order suppressor T cells (Ts2). Comparison of suppressor T cells induced by antigen (Ts1) with Ts2 induced by TsF1 revealed that Ts1 were afferent suppressors active only when given at the time of antigen priming, and not thereafter, whereas Ts2 could act when transferred at any time up to 1 d before antigen challenge for a delayed-type hypersensitivity response. This was true even when the recipient could be shown to be fully immune before transfer of Ts2, thus defining these cells as efferent suppressors. The anti-idiotypic specificity of the Ts2 was demonstrated by the ability of Ts to bind to idiotype (cross-reactive idiotype [CRI])-coated Petri dishes. A soluble extract from Ts2 (TsF2) was also capable of mediating efferent suppression that was functionally antigen- (ABA) specific. Comparison of TsF1 with this new factor, TsF2, revealed that both lack Ig-constant-region determinants, possess H-2-coded determinants, and show specific binding (to ABA and to CRI+-Ig, respectively). TsF1 acts in strains that differ with respect to H-2 and background genes, whereas TsF2 shows H-2- and non-H-2-linked genetic restrictions. This existence of H-2 restriction of TsF2 activity suggests that the apparent discrepancies in studies of H-2 restriction of TsF may be a result of the analysis of two separate classes of TsF, only one of which shows genetically restricted activity, thus unifying several models of suppressor cell activity.

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 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 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 suppression in the transfer of contact sensitivity. Analysis of an I-J+ molecule required for Ly2 suppressor cell activity.

1983 ◽  
Vol 158 (6) ◽  
pp. 1822-1835 ◽  
Author(s):  
W Ptak ◽  
R K Gershon ◽  
P M Flood
Keyword(s):  
T Cells ◽  
Cell Activity ◽  
Suppressor Cell ◽  
Suppressive Activity ◽  
Contact Sensitivity ◽  
Suppressor Factor ◽  
Functional Activities ◽  
A Cell ◽  
Adoptive Immunity

The passive transfer of contact sensitivity (CS) by immune cells can be inhibited with an antigen-specific T suppressor factor. This factor is composed of two subfactors: an antigen-specific subfactor made by an Ly1+ cell (PC1-F) and a antigen nonspecific subfactor made by an Ly2+ T cell (TNBSA-F). The suppressive activity of the complete factor can be eliminated by depleting the assay population of Ly2+ cells, even though it is the Ly1+ cell in the population that transfers the adoptive immunity. This suggests that the Ly2+ cell in the assay population is needed to transduce the suppressive signal to the Ly1+ effector cell of DTH. We found that an Ly2+ cell from immune animals could be induced to produce a cell free subfactor that overcame the requirement for this Ttrans cell in the suppression of CS by TsF. The induction required only PC1-F, TNP-coupled spleen cells, and resulted in the production of an antigen-nonspecific I-J+ subfactor by immune Ly2+, I-J+ cells. The need for the Ly2+ transducer cell could also be overcome by addition of an I-J+ molecule secreted by Ly1 T cells hyperimmunized to SRBC. A suppressor complex made from mixing the I-J+ molecule with TNBSA-F could directly suppress the functional activity of immune T cells not only to transfer CS, but also to deliver help to B cells in an in vitro PFC response. This suppressive complex is antigen-nonspecific and does not require Ly2+ T cells in the assay population for suppressive activity. These results indicate that effector factors of the suppressor circuit require two molecules; one that contains the functional suppressor material and one that serves as a "schlepper," a molecule needed to deliver the suppression to the appropriate target cell. The ability to construct a functional suppressor complex from two subfactors raised against different antigens, using different immunization procedures, which were isolated from factors exhibiting different functional activities suggests that certain cells of the immune system may play a universal role in "transducing" the suppressive signal.

scholarly journals A mechanism responsible for the induction of H-2 restricted second order suppressor T cells.

1983 ◽  
Vol 157 (6) ◽  
pp. 1726-1735 ◽  
Author(s):  
I Aoki ◽  
M Minami ◽  
M E Dorf
Keyword(s):  
T Cells ◽  
Cell Lineage ◽  
Suppressor Cells ◽  
Suppressor Cell ◽  
Second Order ◽  
Suppressor T Cells ◽  
Suppressor Factor ◽  
Splenic Cells ◽  
Specialized Population ◽  
Population Controls

The mechanism by which I-J restrictions were imposed on second-order suppressor cells (Ts2) was analyzed. The induction of Ts2 cells requires presentation of an inducer suppressor factor by a specialized population of factor-presenting cells. The I-J phenotype of this factor-presenting population controls the H-2 restriction of the Ts2 cells. The splenic cells responsible for presenting inducer factor appear to be of macrophage or dendritic cell lineage. Several homologies exist between the mechanism responsible for the induction of H-2-restricted suppressor and helper T cells. Thus, the I region products on specialized presenting cells determine the specificity and genetic restrictions of the T cell. In an H-2 heterozygous F1 animal, two distinct populations of cells can be induced, one specific for each parental H-2 heplotype. Furthermore, the data suggest that the suppressor cells also bear receptors for self H-2 products. The ramifications of these observations for the suppressor cell cascade are discussed.

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.

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.

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