scholarly journals Haplotype-specific suppression of antibody responses in vitro. II. Suppressor factor produced by T cells and T cell hybridomas from mice treated as neonates with semiallogeneic spleen cells.

1981 ◽  
Vol 154 (1) ◽  
pp. 48-59 ◽  
Author(s):  
C M Sorensen ◽  
C W Pierce
Keyword(s):  
T Cells ◽  
T Cell ◽  
Antibody Responses ◽  
Spleen Cells ◽  
Suppressor T Cells ◽  
Cytotoxic Lymphocyte ◽  
Suppressor Factor ◽  
Lymphocyte Responses ◽  
Specific Suppressor T Cells

Culture supernatant fluids from spleen cells from C57BL/10 or BALB/c mice neonatally treated with semiallogeneic (B 10.D2 x B10)F1 cells to induce haplotype-specific suppressor T cells and restimulated with macrophages syngeneic at I-A with the allogeneic haplotype encountered as neonates contain a soluble factor capable of suppressing primary in vitro antibody responses of normal syngeneic spleen cells in a non-antigen-specific manner. This haplotype-specific suppressor factor, TsF-H, has also been recovered in culture fluids of a T cell hybridoma produced by fusion of the AKR thymoma BW5147 and the haplotype-specific suppressor T cells. TsF-H is inactivated by low pH (3.5) trypsin, for 30 min at 50 degrees C, and has a molecular weight in the range of 45,000 to 68,000. Studies with specific immunoabsorbents demonstrate the presence of determinants encoded by the I-A subregion of the haplotype of the T cell producing TsF-H but not I-J subregion or immunoglobulin constant-region determinants on the TsF-H. Suppression is restricted to primary in vitro antibody responses, and not secondary antibody, mixed lymphocyte, or cytotoxic lymphocyte responses by spleen cells syngeneic at the I-A subregion of H-2 with the T cell producing the factor. The properties and activities of TsF-H and the haplotype-specific suppressor T cell are compared and contrasted with antigen-specific and genetically restricted suppressor T cells and their factors.

scholarly journals Haplotype-specific suppression of antibody responses in vitro. I. Generation of genetically restricted suppressor T cells by neonatal treatment with semiallogeneic spleen cells

1981 ◽  
Vol 154 (1) ◽  
pp. 35-47 ◽  
Author(s):  
CM Sorensen ◽  
CW Pierce
Keyword(s):  
T Cells ◽  
Time Course ◽  
Antibody Responses ◽  
Primary Antibody ◽  
Spleen Cells ◽  
Suppressor T Cells ◽  
Cytotoxic Lymphocyte ◽  
Necessary And Sufficient ◽  
Lymphocyte Responses

C57BL/10 mice were injected with semiallogeneic (B10.D2 X C57BL/10)F(1) spleen cells via the anterior facial vein within 24 h of birth to induce tolerance to B10.D2 (H-2(d)) alloantigens. Spleen cells from these mice as adults developed reduced, but significant, mixed lymphocyte and cytotoxic lymphocyte responses in vitro to H-2(d) stimulator cells and these treated mice rejected first-set B10.D2 skin grafts within a normal time-course, indicating that at best only a state of partial tolerance had been induced. Spleen cells from these mice failed to develop antibody responses to a variety of antigens in vitro when H-2(d) macrophages were in the cultures. Partially purified T cells from these neonatally treated mice suppressed primary antibody responses by normal syngeneic spleen cells in the presence of H-2(d) but not other allogeneic macrophages. These radiosensitive, haplotype-specific suppressor T (Ts) cells inhibited primary antibody responses by blocking initiation of the response, but failed to suppress secondary antibody responses and mixed lymphocyte or cytotoxic lymphocyte responses by appropriate responding spleen cells. To activate H-2(d) haplotype-specific Ts cells, stimulation with IA(d) subregion antigen(s) was necessary and sufficient; syngenicity at the I-A subregion of H-2 between the activated Ts cells and target responding spleen cell populations was also necessary and sufficient to achieve suppression. Comparable results have been obtained with spleen cells from BALB/c mice injected as neonates with (B10.D2 × C57BL/10)F(1) spleen cells where IA(b) antigens activate the haplotype-specific Ts cells. Implications for the significance of this population of haplotype-specific Ts cells in immune regulation are discussed and the properties of these Ts cells are compared and contrasted with other antigen-specific and nonspecific Ts cells whose activity is restricted by I- region products.

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 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 Suppression of antibody and T cell proliferative responses to L-glutamic acid60-L-alanine30-L-tyrosine10 by a specific monoclonal T cell factor.

1980 ◽  
Vol 152 (1) ◽  
pp. 235-240 ◽  
Author(s):  
J A Kapp ◽  
B A Araneo ◽  
B L Clevinger
Keyword(s):  
T Cells ◽  
Lymph Node ◽  
T Cell ◽  
Bovine Serum Albumin ◽  
Bovine Serum ◽  
Spleen Cells ◽  
Suppressor T Cells ◽  
Suppressor Factor ◽  
T Cell Factor ◽  
Specific Suppressor T Cells

The synthetic terpolymer L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT) stimulates GAT-specific suppressor T cells in nonresponder mice. Extracts from these T cells contain a GAT-specific soluble T cell suppressor factor (GAT-TsF) that inhibits development of GAT-specific plaque-forming cell (PFC) responses by spleen cells from nonresponder mice stimulated with GAT complexed to methylated bovine serum albumin (GAT-MBSA). These extracts also contain a factor that inhibits development of GAT-specific proliferative responses by GAT-MBSA-primed, nonresponder lymph node T cells. Experiments reported in this manuscript show that a hybrid T cell line, produced by fusion of the AKR thymoma, BW5147, with spleen cells that contain GAT-specific suppressor T cells, produces a constitutive GAT-specific suppresor factor that functionally and serologically resembles GAT-TsF extracted from T cells. More importantly, both GAT-specific PFC and T cell proliferative responses are inhibited by this factor.

scholarly journals Antigen-specific suppression in genetic responder mice to L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT). Characterization of conventional and hybridoma-derived factors produced by suppressor T cells from mice injected as neonates with syngeneic GAT macrophages.

1982 ◽  
Vol 156 (6) ◽  
pp. 1691-1710 ◽  
Author(s):  
C M Sorensen ◽  
C W Pierce
Keyword(s):  
T Cells ◽  
Gel Filtration ◽  
Spleen Cells ◽  
Suppressor T Cells ◽  
Antigen Binding Site ◽  
Suppressor Factor ◽  
Specific Suppressor T Cells ◽  
Early Phases

Spleen cells from C57BL/10 mice injected with syngeneic B10 L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT)-pulsed macrophages (GAT-M phi) within 18 h of birth were unable to respond to soluble GAT, GAT-methylated bovine serum albumin, or B10 GAT-M phi as adults. Spleen cells from these neonatally treated mice responded at control levels to GAT presented in allogeneic M phi and to sheep erythrocytes. Partially purified T cells from these neonatally treated mice suppressed responses by syngeneic virgin, but not primed, spleen cells in an antigen-specific manner and acted during the early phases of the response. These responder GAT-specific suppressor T cells (GAT-TSR) were sensitive to anti-Thy-1 + C and 500-rad irradiation and have the phenotype Ly-1-2+, I-J+; GAT-TSR cells can only suppress responses by spleen cells syngeneic with the GAT-TSR cells at the I-J subregion of H-2. Restimulation of these Ts cells with syngeneic GAT-M phi induces an antigen-specific suppressor factor within the supernatant fluid. The factor, GAT-TsFR, is a glycoprotein with a molecular weight between 48,000 and 63,000, as determined by gel filtration chromatography using isotonic buffers; it bears serologically detectable determinants encoded by the I-J subregion of the H-2 complex, has an antigen-binding site for GAT and L-glutamic acid50-L-tyrosine50, and shares idiotypic determinants with anti-GAT antibodies. The presence of GAT-TsFR in the first 36 h of in vitro culture is required for significant suppression. Furthermore, only responses by spleen cell syngeneic with the cells producing GAT-TsFR at the I-J subregion are suppressed. The fusion of GAT-TsFR-producing cells with BW5147 resulted in generation of two hybridomas with properties and characteristics identical to those of the conventional GAT-TsFR with one exception: conventional and hybridoma 372.D6.5 GAT-TsFR only suppress responses by spleen cells of the I-Jb haplotype, whereas suppression mediated by the second hybridoma GAT-TsFR (372.B3.5) is genetically unrestricted. These hybridoma GAT-TsFR are compared with nonresponder GAT-Ts factor (GAT-TsF) and these responder and nonresponder GAT-TsF are considered in the context of suppressor pathways.

scholarly journals Immunosuppressive factor(s) extracted from lymphoid cells of nonresponder mice primed with L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT) II. Cellular source and effect on responder and nonresponder mice.

1977 ◽  
Vol 145 (4) ◽  
pp. 828-838 ◽  
Author(s):  
J A Kapp ◽  
C W Pierce ◽  
B Benacerraf
Keyword(s):  
T Cells ◽  
Lymphoid Cells ◽  
Antibody Responses ◽  
Spleen Cells ◽  
Suppressor T Cells ◽  
Immunosuppressive Factor ◽  
Cellular Source ◽  
Dose Dependent ◽  
Specific Suppressor T Cells

The synthetic terpolymer of L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT) fails to stimulate development of GAT-specific antibody responses in nonresponder strains of mice, but does stimulate the development of GAT-specific suppressor T cells that inhibit the development of normal anti-GAT antibody responses to GAT complexed to methylated bovine serum albumin (GAT-MBSA). Furthermore, extracts prepared from lymphoid cells of GAT-primed, but not control, nonresponder mice inhibit the development of antibody responses to GAT-MBSA by normal nonresponder mice. This suppression is specific, dose-dependent, and can be readily analyzed in vitro. The suppressive factor is a T-cell product. An extract from GAT-primed DBA/1 mice inhibits the response to GAT-MBSA by spleen cells from histoincompatible strains of mice that are nonresponders to GAT, but not strains that are responders to GAT.

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- 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 T-cell regulation of antibody responses: demonstration of allotype-specific helper T cells and their specific removal by suppressor T cells.

1976 ◽  
Vol 144 (2) ◽  
pp. 330-344 ◽  
Author(s):  
L A Herzenberg ◽  
K Okumura ◽  
H Cantor ◽  
V L Sato ◽  
F W Shen ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Antibody Responses ◽  
Helper T Cells ◽  
Spleen Cells ◽  
Suppressor T Cells ◽  
Effector Cells ◽  
T Cell Regulation ◽  
The Difference

Allotype suppressor T cells (Ts) generated in SJL X BALB/c mice specifically suppress production of antibodies marked with the Ig-1a allotype. The studies presented here show that allotypes Ts suppress by specifically removing helper T cell (Th) activity required to facilitate differentiation and expansion of B cells to Ig-1b antibody-forming cells. We show first that Ts and Th belong to different T-cell subclasses as defined by Ly surface antigens. Ts are Ly2+Lyl- and thus belong to the same subclass as cytotoxic precursor and effector cells; Th are Lyl+Ly2- cells and thus belong to the subclass containing cells which can exert helper functions and initiate delayed hypersensitivity reactions. Placing these cells in these two subclasses shows that Th are different from Ts and suggests that they play different roles in regulating antibody responses. The difference in these roles is defined by the evidence presented here showing that Ts attack Th and regulate the antibody response by specifically regulating the availability of Th activity. We show that in allotype suppressed mice, Ts which suppress Ig-1b antibody production have completely removed the Th activity of helping Ig-1b cells without impairing Th activity which helps other IgB B cells. These findings imply the existence of allotype-specific Th for Ig-1b cells (Ig-1b Th). We directly establish that Ig-1b cells require such help by showing that carrier-primed spleen cells from Iga/Iga congenic hybrids help Ig-1a B cells from hapten-primed Igb/Iga donors but do not help Ig-1b B cells from the same donor in the same adoptive recipient.

scholarly journals Immunosuppressive factor(s) specific for L-glutamic acid(50)-L- tyrosine(50) (GT). II. Presence of I-J determinants on the GT-suppressive factor

1977 ◽  
Vol 146 (1) ◽  
pp. 287-292 ◽  
Author(s):  
J Theze ◽  
C Waltenbaugh ◽  
ME Dorf ◽  
B Benacerraf
Keyword(s):  
T Cells ◽  
Glutamic Acid ◽  
Inbred Mouse ◽  
Inbred Mouse Strain ◽  
Antibody Responses ◽  
Mouse Strains ◽  
Suppressor T Cells ◽  
Suppressor Factor

The responses to the synthetic antigens, L-glutamic acid(60)-L- alanine(30)-L-tyrosine(10) (GAT) and L-glutamic acid(50)-L-tyrosine(50) (GT) are controlled by genes in the I region of the mouse H-2 complex (1-3). Preimmunization of the mice bearing the H-2(p,q,s) nonresponder haplotypes with GAT stimulates the development of suppressor T cells that inhibit in vivo or in vitro antibody responses to GAT complexed to the immunogenic carrier, methylated bovine serum albumin (GAT-MBSA) (4). The copolymer GT is not immunogenic in any inbred mouse strain tested, and has a suppressive effect on the antibody responses to GT-MBSA in mouse strains bearing the H-2(d,f,k,s) haplotypes; suppressor T cells have been demonstrated to be responsible for specific GT suppression (3). We have obtained specific suppressive extracts from thymus and spleen cells of GAT-or GT-primed suppressor strains (5,6). The specific suppressive T-cell factors in the active extracts have been characterized (6,7) and appear similar to the carrier-specific suppressor factor described by Tada and Taniguchi (8). These products belong to a family of newly identified molecules coded for by the I region of the H-2 complex with affinity for antigen and helper (9,10) or suppressive (5-8) regulatory activity on the immune response. Recently, Tada et al. have reported that the keyhole limpet hemocyanin (KLH)-specific suppressor factor is coded for by the I-J subregion of the H-2 complex (11). We now demonstrate also that a GT-specific suppressor factor extracted from the spleens and thymuses of B10.BR (H-2(k)) mice bears determinants controlled by the I-J subregion of the H-2 complex.

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