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 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 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 Immunosuppressive factor(s) specific for L-glutamic acid50-L-tyrosine50 (GT). III. Generation of suppressor T cells by a suppressive extract derived from GT-primed lymphoid cells.

1977 ◽  
Vol 146 (4) ◽  
pp. 970-985 ◽  
Author(s):  
C Waltenbaugh ◽  
J Thèze ◽  
J A Kapp ◽  
B Benacerraf
Keyword(s):  
T Cells ◽  
Suppressor Cells ◽  
Lymphoid Cells ◽  
Spleen Cells ◽  
Suppressor T Cells ◽  
T Cell Factor ◽  
Immunosuppressive Factor ◽  
Step Model ◽  
Specific Suppressor T Cells ◽  
T Suppressor Cells

Injection of mice with L-glutamic acid50-L-tyrosine50 (GT)- or L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT)-specific suppressor T-cell factor (GT-TsF or GAT-TsF) up to 5 wk before antigenic challenge challenge suppresses GT-methylated bovine serum albumin (MBSA) and GAT-MBSA plaque-forming cells responses. T suppressor cells are responsible for the suppression induced by the suppressive extract as demonstrated by adoptive transfer and sensitivity to anti-Thy-1 and complement treatment. We conclude that suppressive extract induces specific suppressor T cells. The material responsible for generation of suppressor T cells is a product of the I subregion of the H-2 complex. We have excluded that suppressive quantities of antigens are present in the extract. A/J mice, which can neither be suppressed by GT nor make GT-TsF can be suppressed by BALB/c GT-tsf. Spleen cells from BALB/c GT TsF-primed A/J mice can adoptively transfer suppression to normal syngeneic recipients. A/J mice appear to be genetically defective in cells involved in factor production. These results are discussed in the light of a two-step model for induction of antigen-specific suppressor cells.

scholarly journals GENETIC CONTROL OF IMMUNE RESPONSES IN VITRO

1974 ◽  
Vol 140 (3) ◽  
pp. 648-659 ◽  
Author(s):  
Judith A. Kapp ◽  
Carl W. Pierce ◽  
Stuart Schlossman ◽  
Baruj Benacerraf
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Immune Responses ◽  
Cell Function ◽  
Suppressor Cells ◽  
Specific Response ◽  
Spleen Cells ◽  
X Irradiation

In recent studies we have found that GAT not only fails to elicit a GAT-specific response in nonresponder mice but also specifically decreases the ability of nonresponder mice to develop a GAT-specific PFC response to a subsequent challenge with GAT bound to the immunogenic carrier, MBSA. Studies presented in this paper demonstrate that B cells from nonresponder, DBA/1 mice rendered unresponsive by GAT in vivo can respond in vitro to GAT-MBSA if exogenous, carrier-primed T cells are added to the cultures. The unresponsiveness was shown to be the result of impaired carrier-specific helper T-cell function in the spleen cells of GAT-primed mice. Spleen cells from GAT-primed mice specifically suppressed the GAT-specific PFC response of spleen cells from normal DBA/1 mice incubated with GAT-MBSA. This suppression was prevented by pretreatment of GAT-primed spleen cells with anti-θ serum plus C or X irradiation. Identification of the suppressor cells as T cells was confirmed by the demonstration that suppressor cells were confined to the fraction of the column-purified lymphocytes which contained θ-positive cells and a few non-Ig-bearing cells. The significance of these data to our understanding of Ir-gene regulation of the immune response is discussed.

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 Suppressor T cells activated in a primary in vitro response to non-major histocompatibility alloantigens.

1982 ◽  
Vol 156 (5) ◽  
pp. 1398-1414 ◽  
Author(s):  
S Macphail ◽  
O Stutman
Keyword(s):  
Mixed Lymphocyte Reaction ◽  
Cytotoxic T Lymphocyte ◽  
Suppressor Cells ◽  
Suppressor Cell ◽  
Spleen Cells ◽  
Suppressor T Cells ◽  
Normal Spleen ◽  
In Vitro Response

Normal mouse spleen cells are not capable of mounting a primary cytotoxic T lymphocyte (Tc) response to non-H-2 alloantigens in vitro, although a good secondary H-2-restricted response is observable after in vivo immunization of the responder animals. Suppressor cells are generated in such a primary responses provided a Mls incompatibility exists between the responder and stimulator. These suppressors are not antigen specific, are Thy-1+, Lyt-1+, 2-, I-J-, and are highly radiosensitive. The suppressor cell precursors in normal spleen express the same phenotype. These suppressor cells are probably implicated in the lack of a primary Tc response in a primary mixed lymphocyte reaction across non-H-2 incompatibilities that include an Mls difference.

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 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 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 Hapten-specific T cell responses to 4-hydroxy-3-nitrophenyl acetyl. XII. Fine specificity of anti-idiotypic suppressor T cells (Ts2).

1981 ◽  
Vol 154 (5) ◽  
pp. 1382-1389 ◽  
Author(s):  
D H Sherr ◽  
S T Ju ◽  
M E Dorf
Keyword(s):  
T Cells ◽  
Suppressor Cells ◽  
Cell System ◽  
Spleen Cells ◽  
Suppressor T Cells ◽  
Fine Specificity ◽  
Cell Responses ◽  
Effector Phase ◽  
Different Levels

The fine specificity of anti-idiotypic, effector-phase suppressor T cells (Ts2) induced by the intravenous injection of syngeneic spleen cells covalently coupled with the 4-hydroxy-3-nitrophenyl acetyl (NP) hapten was studied in an in vitro plaque-forming cell system. By comparing the ability of these suppressor cells to bind monoclonal anti-NP antibodies that express different levels of serologically detected NPb idiotypic determinants, it was shown that anti-idiotypic suppressor T cells do not recognize the predominant NPb idiotypic determinants that are defined by serologic analysis. The implications for the possible expression and/or recognition of different sets of idiotypic determinants on T and B cells are discussed.

Sign in / Sign up

Export Citation Format

Share Document