scholarly journals BIOLOGICAL EXPRESSIONS OF LYMPHOCYTE ACTIVATION

1973 ◽  
Vol 137 (2) ◽  
pp. 205-223 ◽  
Author(s):  
Robert R. Rich ◽  
Carl W. Pierce
Keyword(s):  
Concanavalin A ◽  
Specific Antigen ◽  
Cell Activity ◽  
Lymphocyte Activation ◽  
Spleen Cells ◽  
Culture Initiation ◽  
Normal Spleen ◽  
Activated T Lymphocytes

The effects of nonspecific phytomitogens on primary plaque-forming cell (PFC) responses of mouse spleen cells to heterologous erythrocytes in vitro were studied. Spleen cell cultures treated with concanavalin A or phytohemagglutinin in vitro or established with spleen cells derived from mice injected with concanavalin A 24 h previously were similarly affected. In both cases, submitogenic doses resulted in substantial enhancement of PFC responses, whereas 10-fold larger doses were profoundly inhibitory. In contrast to the suppressive effects of mitogenic doses of phytomitogens added at culture initiation, addition of these same doses to cultures 48 h later resulted in increased PFC responses. This enhancement could be observed within 1 h after treatment and consequently could not be ascribed only to mitotic expansion of the antibody-synthesizing clone. Activation of spleen cells with specific antigen before mitogen treatment was not required for expression of the enhancing or suppressing effects on PFC responses. IgM and IgG PFC responses were similarly affected. Studies of cell interactions revealed that as few as 105 spleen cells obtained from mice treated with concanavalin A in vivo synergistically enhanced the PFC responses of 107 normal spleen cells. This enhancement was mediated by mitogen-activated T lymphocytes which were resistant to 2000 R irradiation 24 h after activation. The relevance of these observations to emerging concepts of helper and suppressor T cell activity is discussed.

scholarly journals Immune responses during pregnancy. Evidence of suppressor cells for splenic antibody response.

1979 ◽  
Vol 150 (4) ◽  
pp. 898-908 ◽  
Author(s):  
K Suzuki ◽  
T B Tomasi
Keyword(s):  
Antibody Response ◽  
Cell Activity ◽  
Suppressor Cells ◽  
Suppressor Cell ◽  
Adherent Cell ◽  
Spleen Cells ◽  
Normal Spleen ◽  
Pregnant Mice

The primary IgM antibody response to sheep erythrocytes in vivo as well as in vitro is markedly decreased in the spleen cells of pregnant mice, compared to age-matched female controls. Decreased antibody synthesis appears to be mediated by nonspecific suppressor cells, because the addition of pregnant spleen cells to the normal spleen cell cultures causes a significant suppression of plaque-forming-cell responses of the normal spleen cells. Suppressor cell activity was not observed in lymph nodes of pregnant mice. At least two populations of pregnant spleen cells were shown to exert a suppressor cell activity; one is T lymphocytes and the other a nylon-adherent cell present in the B-cell-enriched macrophage-depleted fraction. Pregnant spleen cells cultured in vitro were shown to secrete a soluble suppressive factor(s) into the supernatant medium.

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 BIOLOGICAL EXPRESSIONS OF LYMPHOCYTE ACTIVATION

1973 ◽  
Vol 137 (3) ◽  
pp. 649-659 ◽  
Author(s):  
Robert R. Rich ◽  
Carl W. Pierce
Keyword(s):  
Cell Population ◽  
Concanavalin A ◽  
Lymphocyte Activation ◽  
Suppressor Cells ◽  
Mouse Spleen ◽  
Spleen Cells ◽  
Cell Responses ◽  
Helper Cells ◽  
X Irradiation

A population of thymus-derived lymphocytes has been identified that, upon activation by the nonspecific plant mitogen concanavalin A, suppresses the development of plaque-forming cell responses in fresh or 48-h antigen-stimulated cultures of mouse spleen cells. Suppressor cells can inhibit both primary and secondary IgM and IgG responses in vitro. X-irradiation before activation of peripheral thymus-derived cells by concanavalin A abrogates generation of suppressor cells. After a 48 h activation period, however, the function of concanavalin A-activated suppressor cells is radioresistant. As yet uncertain is whether these suppressor cells are a population of cells distinct from thymus-derived "helper" cells. In certain important regards, the cells mediating these two opposing functions share similar characteristics; the effect observed may be determined by the circumstances of activation or the numbers of activated cells, and may consequently represent different functions of a single thymus-derived regulator cell population.

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.

Blocking the regulatory T cell molecule LAG-3 augments in vivo anti-tumor immunity in an autochthonous model of prostate cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 2573-2573
Author(s):  
C. G. Drake ◽  
C. Kelleher ◽  
T. Bruno ◽  
T. Harris ◽  
D. Flies ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
T Cells ◽  
T Cell ◽  
Regulatory T Cell ◽  
Specific Antigen ◽  
Cell Activity ◽  
Cd8 T Cell ◽  
Regulatory Function

2573 Background: LAG-3 is a CD4 homolog expressed on activated T cells, NK cells, tumor infiltrating lymphocytes (TIL), and plasmacytoid dendritic cells. Recently, we showed that LAG-3 was relatively overexpressed in specific T cells rendered unresponsive in vivo by the presence of cognate self-antigen. These anergic T cells display regulatory function both in vitro and in vivo, and blockade of LAG-3 with a non-depleting monoclonal antibody significantly mitigates their regulatory T cell activity. Methods: Using a novel model of prostate cancer in which a tumor-specific antigen is expressed in autochthonous tumors, we tested whether treatment with a non-depleting anti-LAG-3 antibody affected trafficking and function of tumor-specific T cells. Results: LAG-3 blockade significantly augments specific CD8 T cell trafficking to antigen-expressing tumors, but not to normal tissue. Most significantly, LAG-3 blockade functionally reversed CD8 T cell tolerance as assayed by an in vivo cytotoxic T lymphocyte (CTL) assay. Combining LAG-3 blockade with specific anti-tumor vaccination results in a dramatic increase in activated CD8 T cells in the tumor parenchyma. Conclusions: Taken together, these data support the concept that treatment with a LAG-3 blocking antibody may significantly delay disease progression in patients with cancer. We have recently generated a panel of monoclonal antibodies directed against human LAG-3; several of these antibodies significantly augment human T cell responses in vitro. No significant financial relationships to disclose.

scholarly journals RAPID BREAKING OF TOLERANCE AGAINST ESCHERICHIA COLI LIPOPOLYSACCHARIDE IN VIVO AND IN VITRO

1972 ◽  
Vol 135 (4) ◽  
pp. 850-859 ◽  
Author(s):  
Olof Sjöberg
Keyword(s):  
Escherichia Coli ◽  
Immune Responsiveness ◽  
Spleen Cells ◽  
E Coli ◽  
Normal Spleen ◽  
Escherichia Coli Lipopolysaccharide ◽  
Tolerant State

The breaking of tolerance against the lipopolysaccharide from E. coli 055:B5 was studied. It was found that immune responsiveness recovered very slowly in vivo, tolerance still existing 3 wk after the last tolerizing injection. However, if spleen cells from tolerant mice were transferred into irradiated syngeneic recipients, the tolerant state was readily broken. Spleen cells transferred 3 days after the last tolerance-maintaining dose did not respond, whereas cells transferred on day 5 or 7 responded equally well as normal spleen cells. It was also possible to break tolerance by incubating tolerant spleen cells, which did not respond after transfer, for 20 hr in vitro before transfer into irradiated recipients. The results suggest that there exist reversibly inactivated cells in tolerant animals and that these cells can be reactivated upon removal of the cells to a neutral environment.

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 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 Antigen-binding T cells as helper cells. Separation of helper cells by immune rosette formation.

1975 ◽  
Vol 142 (4) ◽  
pp. 1035-1039 ◽  
Author(s):  
S Kontiainen ◽  
L C Andersson
Keyword(s):  
T Cells ◽  
Gamma Globulin ◽  
Specific Antigen ◽  
Cell Activity ◽  
Velocity Sedimentation ◽  
Antigen Binding ◽  
Spleen Cells ◽  
Helper Cells ◽  
Helper Activity

The spleen T cells from mice immunized 6 days earlier with either chicken gamma globulin (CGG) or with donkey erythrocytes (DRC) were rosetted with CGG-coated sheep erythrocytes or with DRC. The immune rosettes (RFC) (antigen-binding cells) were separated from the bulk of nonrosette-forming cells (non-RFC) by 1-g velocity sedimentation and the RFC and non-RFC tested for helper activity in cooperative antihapten responses in vitro. RFC or non-RFC were mixed with normal or hapten-primed spleen cells, challenged with the appropriate hapten-carrier conjugate and cultured for 4 days in Marbrook tissue cultures. The helping activity was quantitated from the numbers of antihapten antibody-producing cells generated per culture. The results show that specific helper cell activity could be selectively recovered in the immune rosette-forming cell population whereas the non-RFC population was depleted of help. These findings indicate that the helper T cells express specific antigen binding receptors.

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