scholarly journals Immunoregulatory circuits that modulate responsiveness to suppressor cell signal. Failure of B10 mice to respond to suppressor factors can be overcome by quenching the contrasuppressor circuit.

1981 ◽  
Vol 153 (6) ◽  
pp. 1547-1561 ◽  
Author(s):  
K Yamauchi ◽  
D R Green ◽  
D D Eardley ◽  
D B Murphy ◽  
R K Gershon
Keyword(s):  
T Cells ◽  
T Cell ◽  
Antibody Response ◽  
Sheep Erythrocyte ◽  
Biologically Active ◽  
Mouse Strains ◽  
Cellular Interactions ◽  
Spleen Cells ◽  
Suppressor Factor

The in vitro antibody response of spleen cells from B10 strain mice is not suppressed by factor preparations made by primed Ly-2 T cells, although these preparations can suppress the in vitro antibody response of spleen cells from other mouse strains (1-3)2. The factor preparations from Ly-2 cells contain at least two separable activities: one that acts as a suppressor moiety (Ly-2 T cell suppressor factor [Ly-2 TsF]) and a second factor that acts as an inducer of contrasuppression (Ly-2 TcsiF); the latter initiates a series of cellular interactions that leads to the inhibition of suppression that we refer to as contrasuppression. Removal of components (either cellular or humoral) of the contrasuppressor circuit makes spleen cells from B10 strain mice as easily suppressible as are those of other mouse strains. Thus, removal of the contrasuppressor inducer cell and/or its biologically active product with the use of an anit-J serum, or removal of the functional acceptor of the inducer cell with the same or other (Ly-2; Qa-1) antisera breaks the B10 suppressor barrier. Contrasuppressive activity. but not helper activity can be eluted from anit-I-J immunoabsorbents. The addition of B10 T cells to either B6 or B10 spleen cell culture deprived of acceptor cells for the TcsiF reconstitutes contrasuppression more efficiently than does the addition of C57BL/6 T cells. Ly-2 TcsiF is more cross-reactive than is Ly-2 TsF so that absorption of factor preparations from sheep erythrocyte-primed Ly-2 cells with horse erythrocytes also breaks the B10 suppressor barrier. The hyperresponsiveness of splenic T cells from B10 strains to Ly-2 TcsiF may be an in vitro exaggeration of a normal in vivo process. Thus it is possible that one can take advantage of this unusual situation to help dissect out the cellular and subcellular components of T cell circuits that moldulate sensitivity to immunoregulatory signals.

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 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 Congenitally athymic nude (nu/nu) mice have Thy-1-bearing immunocompetent helper T cells in their peritoneal cavity.

1980 ◽  
Vol 151 (4) ◽  
pp. 965-968 ◽  
Author(s):  
H Ishikawa ◽  
K Saito
Keyword(s):  
T Cells ◽  
Lymph Node ◽  
Guinea Pig ◽  
Antibody Response ◽  
Sheep Erythrocyte ◽  
Helper T Cells ◽  
Spleen Cells ◽  
Lymph Node Cells ◽  
Pig Serum

Heavily irradiated peritoneal cells (PC) from congenitally athymic nude (nu/nu) mice markedly restored the impaired in vitro antibody response of nu/nu spleen cells to sheep erythrocyte antigens (T-dependent antigen), whereas irradiated spleen or lymph node cells from nu/nu mice had no effect on the response. This activity of the irradiated PC of nu/nu mice was completely abolished by treatment with anti-Thy-1.2 antiserum plus normal guinea pig serum (C') and is, therefore, attributable to a function of matured T cells.

scholarly journals Suppression of FVIII Antibody Production By FVIII BAR T-Cell in Vitro in the Presence of Inhibitors

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3789-3789
Author(s):  
Kalpana Parvathaneni ◽  
Ai-Hong Zhang ◽  
David W. Scott
Keyword(s):  
T Cells ◽  
T Cell ◽  
Antibody Response ◽  
B Cell ◽  
Cd8 T Cells ◽  
Conflicts Of Interest ◽  
Spleen Cells ◽  
Engineered T Cells

Abstract To modulate B-cell responsiveness to FVIII, we previously generated cytotoxic cells expressing FVIII C2 or A2 immunodominant domains as chimeric receptors. We termed these antigen-expressing engineered T cells, "BARs", for B-cell Antibody Receptor. These CD8 T cells directly interact and kill FVIII-specific B cells and anti-FVIII hybridomas in prophylactic experiments in vitro and in vivo. It was not known whether these BAR CD8s could function or would be blocked in the presence of circulating antibodies to the expressed BAR domains. To test this, we cultured FVIII C2 or A2 BAR CD8 T cell with a mixture of monoclonal antibodies specific for these domains (up to 10 BU), and then added them to spleen cells from FVIII-immunized mice. These spleen cells were then re-stimulated with FVIII and the antibody response was determined after 5 days. Our results showed that these BAR CD8 T cells were not blocked in their ability to suppress the antibody response to FVIII under these conditions. Coupled with the observation that BAR-T cells can be stimulated to proliferate by anti-FVIII monoclonals, these results suggest that BAR cytotoxic activity may still be effective in the presences of inhibitors. (Supported by NIH grant R01 HL126727) Disclosures No relevant conflicts of interest to declare.

scholarly journals Mechanisms of Ly2 suppressor cell activity. Activation of an Ly1 I-J+ cell is required to transduce the suppressive signal.

1984 ◽  
Vol 159 (5) ◽  
pp. 1413-1428 ◽  
Author(s):  
P M Flood ◽  
D C Louie
Keyword(s):  
T Cells ◽  
Genetic Polymorphisms ◽  
Target Cell ◽  
Cell Activity ◽  
Suppressor Cell ◽  
Cellular Interactions ◽  
Spleen Cells ◽  
Suppressor Factor ◽  
In Vitro Response

A cell-free product secreted by Ly1-2+ T cells (Ly2 TsF) can suppress the in vitro response to sheep erythrocytes (SRBC) of spleen cells depleted of Ly2+ T cells. This suppressor factor expresses biological activity only when the acceptor cells share major histocompatibility complex (MHC)-linked polymorphic genes with the cells that made the Ly2 TsF. Removal of Ly1 I-J+ cells from the assay culture abrogates the ability of Ly2 TsF to suppress these cultures, but we can replace the need for the I-J+ cells in the assay culture with an I-J+ soluble factor derived from them. We investigated the cellular interactions involved in the activation of I-J+ cells by Ly2 TsF in vitro. We have been able to induce the production of an I-J+ molecule needed for Ly2 TsF activity in a 48-h intermediate culture of B cell-depleted Ly1 spleen cells, Ly2 TsF, and antigen. This molecule not only fails to bind antigen, but is also antigen nonspecific in that it can be induced by Ly2 TsF of irrelevant specificities. In order to replace the activity of the Ly1 I-J+ cell in the assay culture, the cell induced by Ly2 TsF to produce the I-J+ molecule in vitro must share genetic polymorphisms linked to the MHC with the Ly2 TsF, and genetic polymorphisms linked to the Igh-V gene complex with the target cell. In order for Ly2 TsF to induce cells of the primary culture to produce the I-J+ molecule, Ly2 TsF must share genetic polymorphisms linked to the IE region of the MHC with the Ly1 I-J+ cell producing the I-J+ molecule. These results indicate that the suppressive mechanism of Ly2 TsF involves the interaction with an Ly1 I-J+ molecule. This I-J+ molecule serves to focus the antigen-specific suppressor molecule on the target cell. The recognition event of this suppressive complex on the surface of the acceptor cell is controlled by Igh-V-linked genes restricted by the I-J+ molecule of the suppressor complex. This suppressor interaction is confined to the suppressor effector phase of the suppressor circuit since the I-J+ molecules needed for by Ly2 TsF activity do not substitute for the I-J+ molecules needed for the activity of Ly1 TsiF , a T cell factor that initiates the suppressor cell circuit.(ABSTRACT TRUNCATED AT 400 WORDS)

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 Positive Selection of γδ CTL by TL Antigen Expressed in the Thymus

1996 ◽  
Vol 184 (6) ◽  
pp. 2175-2184 ◽  
Author(s):  
Kunio Tsujimura ◽  
Toshitada Takahashi ◽  
Akimichi Morita ◽  
Hitomi Hasegawa-Nishiwaki ◽  
Shigeru Iwase ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Positive Selection ◽  
Transgenic Mouse ◽  
Mouse Strains ◽  
Skin Grafts ◽  
Spleen Cells ◽  
C3h Mice ◽  
Ctl Activity ◽  
Selection Of

To elucidate the function of the mouse TL antigen in the thymus, we have derived two TL transgenic mouse strains by introducing Tlaa-3 of A strain origin with its own promoter onto a C3H background with no expression of TL in the thymus. These transgenic mouse strains, both of which express high levels of Tlaa-3-TL antigen in their thymus, were analyzed for their T cell function with emphasis on cytotoxic T lymphocyte (CTL) generation. A T cell response against TL was induced in Tg.Tlaa-3-1, Tg.Tlaa-3-2, and control C3H mice by skin grafts from H-2Kb/T3b transgenic mice, Tg.Con.3-1, expressing T3b-TL ubiquitously. Spleen cells from mice that had rejected the T3b-TL positive skin grafts were restimulated in vitro with Tg.Con.3-1 irradiated spleen cells. In mixed lymphocyte cultures (MLC), approximately 20% and 15% of Thy-1+ T cells derived from Tg.Tlaa-3-1 and Tg.Tlaa-3-2, respectively, expressed TCRγδ, whereas almost all those from C3H expressed TCRαβ. The MLC from Tg.Tlaa-3-2 and C3H demonstrated high CTL activity against TL, while those from Tg.Tlaa-3-1 had little or none. The generation of γδ CTL recognizing TL in Tg.Tlaa-3-2, but not C3H mice, was confirmed by the establishment of CTL clones. A total of 14 γδ CTL clones were established from Tg.Tlaa-3-2, whereas none were obtained from C3H. Of the 14 γδ CTL clones, 8 were CD8+ and 6 were CD4−CD8− double negative. The CTL activity of all these clones was TL specific and inhibited by anti-TL, but not by anti-H-2 antibodies, demonstrating that they recognize TL directly without antigen presentation by H-2. The CTL activity was blocked by antibodies to TCRγδ and CD3, and also by antibodies to CD8α and CD8β in CD8+ clones, showing that the activity was mediated by TCRγδ and coreceptors. The thymic origin of these γδ CTL clones was indicated by the expression of Thy-1 and Ly-1 (CD5), and also CD8αβ heterodimers in CD8+ clones on their surfaces and by the usage of TCR Vγ4 chains in 12 of the 14 clones. Taken together, these results suggest that Tlaa-3-TL antigen expressed in the thymus engages in positive selection of a sizable population of γδ T cells.

scholarly journals Acceptor-suppressor T cell hybridoma with a receptor recognizing antigen-specific suppressor factor.

1983 ◽  
Vol 158 (6) ◽  
pp. 1912-1923 ◽  
Author(s):  
I Takei ◽  
T Sumida ◽  
M Taniguchi
Keyword(s):  
T Cells ◽  
T Cell ◽  
Antibody Response ◽  
Keyhole Limpet Hemocyanin ◽  
Acceptor Site ◽  
Suppressor Factor ◽  
T Cell Factor ◽  
Suppressor T Cell ◽  
Antigen System ◽  
Petri Dishes

An acceptor hybridoma with a receptor that recognizes the keyhole limpet hemocyanin (KLH)-specific suppressor T cell factor (KLH-TsF) was established after the fusion of C57BL/6 splenic T cells enriched with KLH-coated petri dishes. The cloned hybridoma (34S-281) could be specifically activated by stimulation with the conventional KLH-TsF or monoclonal KLH-TsF from three different hybridomas in the absence of the relevant antigen (KLH) and it started to produce another factor that suppresses the antibody response against DNP-KLH in a KLH-specific fashion. The KLH specificity of the TsF was required for activation. The new factor was found not to bind the KLH but to be absorbed with the KLH-TsF-producing hybridoma. It is thus strongly suggested that the acceptor site has a complementary structure (antiidiotype) for the KLH-TsF. Moreover, the idiotypic determinant on KLH-TsF was found to have a structure similar to that on some of the anti-KLH antibodies, since the acceptor hybridoma was specifically killed by the conventional anti-KLH antibodies and complement. Drawing on the above results, the idiotype-antiidiotype network in the conventional antigen system is discussed.

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