scholarly journals Haplotype-specific suppression of cytotoxic T cell induction by antigen inappropriately presented on T cells.

1983 ◽  
Vol 157 (1) ◽  
pp. 141-154 ◽  
Author(s):  
P J Fink ◽  
I L Weissman ◽  
M J Bevan
Keyword(s):  
T Cells ◽  
Cytotoxic T Lymphocyte ◽  
Mixed Lymphocyte Culture ◽  
Lymphocyte Culture ◽  
Cytotoxic T Cell ◽  
Spleen Cells ◽  
Specific Suppression ◽  
Veto Cells

To detect a strong cytotoxic T lymphocyte (CTL) response to minor histocompatibility (H) antigens in a 5-d mixed lymphocyte culture, it is necessary to use a responder that has been primed in vivo with antigen-bearing cells. It has previously been shown that minor-H-specific CTL can be primed in vivo both directly by foreign spleen cells and by presentation of foreign minor H antigens on host antigen-presenting cells. This latter route is evident in the phenomenon of cross-priming, in which H-2 heterozygous (A x B)F1 mice injected 2 wk previously with minor H-different H-2A (A') spleen cells generate both H-2A- and H-2B-restricted minor-H-specific CTL. In a study of the kinetics of direct- vs. cross-priming to minors in F1 mice, we have found that minor H-different T cells actually suppress the induction of virgin CTL capable of recognizing them. CTL activity measured from F1 mice 3-6 d after injection with viable A' spleen cells is largely H-2B restricted. The H-2A-restricted response recovers such that roughly equal A- and B-restricted activity is detected in mice as early as 8-10 d postinjection. This temporary hyporeactivity does not result from generalized immunosuppression--it is specific for those CTL that recognize the foreign minor H antigen in the context of the H-2 antigens on the injected spleen cells. The injected spleen cells that mediate this suppression are radiosensitive T cells; Lyt-2+ T cells are highly efficient at suppressing the induction of CTL in vivo. No graft vs. host reaction by the injected T cells appears to be required, as suppression of direct primed CTL can be mediated by spleen cells that are wholly tolerant of both host H-2 and minor H antigens. Suppression cannot be demonstrated by in vitro mixing experiments. Several possible mechanisms for haplotype-specific suppression are discussed, including inactivation of responding CTL by veto cells and in vivo sequestration of responding CTL by the injected spleen cells.

scholarly journals The effect of allogeneic presensitization on H-Y graft survival and in vitro cell-mediated responses to H-y antigen.

1976 ◽  
Vol 144 (3) ◽  
pp. 810-820 ◽  
Author(s):  
R D Gordon ◽  
B J Mathieson ◽  
L E Samelson ◽  
E A Boyse ◽  
E Simpson
Keyword(s):  
Mixed Lymphocyte Culture ◽  
Lymphocyte Culture ◽  
The Other ◽  
Target Cells ◽  
Spleen Cells ◽  
Cytotoxic Cells ◽  
Parental Haplotype ◽  
Cytotoxic Responses

C57BL/6 and C57BL/10 female mice were grafted with skin from male or female donors incompatible for H-2 and/or non-H-2 antigens. Syngeneic male grafts applied after the rejection of primary allografts or syngeneic male grafts were rejected in accelerated (second set) fashion, whereas male grafts applied after primary female grafts were not. In addition, C57BL/10 female spleen cells, primed in vivo with an allogeneic (BALB/c, CBA, or B10.BR) male graft and challenged in vitro in mixed lymphocyte culture with syngeneic (C57BL/10) male cells, produced cytotoxic cells specific for syngeneic male target cells. We conclude that at least some component of H-Y is detected by female responder cells on allogeneic male cells, and that the second set cell mediated response to H-Y is not necessarily restricted by the H-2 haplotype of the primary sensitizing strain. Moreover, (CBA X B10) F1 females, primed in vivo with male cells of one parental haplotype (B10 or CBA) and challenged in vitro with male cells of the other parental haplotype (CBA or B10), fail to lyse male target cells of either parental haplotype. It therefore seems unlikely that a helper determinant shared between B10 and CBA is sufficient to explain the ability of CBA male cells to prime H-2-restricted T-cell cytotoxic responses by B10 females.

Stimulation of dendritic cells via the dectin-1/Syk pathway allows priming of cytotoxic T-cell responses

Blood ◽  
2008 ◽  
Vol 112 (13) ◽  
pp. 4971-4980 ◽  
Author(s):  
Salomé LeibundGut-Landmann ◽  
Fabiola Osorio ◽  
Gordon D. Brown ◽  
Caetano Reis e Sousa
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Cd8 T Cells ◽  
Cytotoxic T Lymphocyte ◽  
Cytotoxic T Cell ◽  
Immune Recognition ◽  
Cytotoxic T Cell Responses ◽  
Ctl Responses

Abstract The C-type lectin receptor dectin-1 functions as a pattern recognition receptor for β-glucans and signals via Syk kinase but independently of the Toll-like receptor (TLR) pathway to regulate expression of innate response genes. Dectin-1 signaling can promote activation of dendritic cells (DCs), rendering them competent to prime Th1 and Th17 responses. Here we show that dectin-1–activated DCs can also prime cytotoxic T-lymphocyte (CTL) responses. DCs exposed to a dectin-1 agonist induced antigen-specific expansion of TCR transgenic CD8+ T cells and their differentiation into CTLs in vitro. Dectin-1 agonist also acted as an adjuvant for CTL crosspriming in vivo, eliciting potent CTL responses that protected mice from tumor challenge. In vitro but not in vivo, CTL crosspriming was dependent on IL-12 p70, which was produced by dectin-1–activated DCs in response to IFN-γ secreted by newly activated CD8+ T cells. The dectin-1/Syk pathway is thus able to couple innate immune recognition of β-glucans to all branches of the adaptive immune system, including CD4+ T-helper cells, B cells, and CD8+ cytotoxic T cells. These data highlight the ability of non-TLR receptors to bridge innate and adaptive immunity and suggest that dectin-1 agonists may constitute useful adjuvants for immunotherapy and vaccination.

scholarly journals Cytotoxic T cells distinguish between trinitrophenyl- and dinitrophenyl-modified syngeneic cells.

1977 ◽  
Vol 146 (2) ◽  
pp. 600-605 ◽  
Author(s):  
J Forman
Keyword(s):  
T Cells ◽  
Cytotoxic Effect ◽  
Cytotoxic T Cells ◽  
Cytotoxic T Cell ◽  
Target Cells ◽  
Spleen Cells ◽  
Competition Assay ◽  
Effector Cells

Spleen cells sensitized against trinitrophenyl (TNP)-modified stimulator cells displayed a cytotoxic effect against syngeneic TNP-modified but not dinitrophenyl (DNP)-modified target cells. The same finding was observed in the opposite direction; that is, effector cells sensitized against DNP-modified stimulator cells did not cross kill TNP-modified targets. The specificity of the anti-TNP effector cells was confirmed in a cold target competition assay. Presensitization in vivo with hapten-modified cells followed by rechallenge and testing in vitro did not alter the specificity of the response between the haptens. These data indicate that the receptor(s) on the cytotoxic T cell can distinguish between two closely related haptenic molecules.

scholarly journals Heterogeneity in the development of cytotoxic T lymphocytes in vitro revealed by sensitivity to hydrocortisone.

1975 ◽  
Vol 142 (3) ◽  
pp. 790-795 ◽  
Author(s):  
A Altman ◽  
I R Cohen
Keyword(s):  
Cytotoxic T Lymphocytes ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Mixed Lymphocyte Culture ◽  
Lymphocyte Culture ◽  
Differential Sensitivity ◽  
Effector Cells ◽  
In Vitro Systems

In the present study we used hydrocortisone (HC) treatment in vivo as a probe to analyze two different in vitro systems for the regeneration of cytotoxic T lymphocyte (CTL), namely the antifibroblast reaction (AFR) and the mixed lymphocyte culture (MLC) system. We found that cells remaining in the thymus after HC treatment had increased reactivity in these two systems. However, the same treatment in the spleen severely depressed the MLC reactivity in both the proliferative and the cytolytic phases, while markedly increasing the AFR reactivity. These findings demonstrate heterogeneity of CTL precursors and/or their pathways of differentiation into effector cells. In addition, MLC-reactive cells in the thymus appear to be distinct from such cells in the spleen, as judged from their differential sensitivity to HC.

scholarly journals Cd40-Independent Pathways of T Cell Help for Priming of Cd8+ Cytotoxic T Lymphocytes

2000 ◽  
Vol 191 (3) ◽  
pp. 541-550 ◽  
Author(s):  
Zhengbin Lu ◽  
Lingxian Yuan ◽  
Xianzheng Zhou ◽  
Eduardo Sotomayor ◽  
Hyam I. Levitsky ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Cytotoxic T Lymphocyte ◽  
Cell Communication ◽  
Cd8 T Cell ◽  
Cd4 Help ◽  
T Cell Help

In many cases, induction of CD8+ CTL responses requires CD4+ T cell help. Recently, it has been shown that a dominant pathway of CD4+ help is via antigen-presenting cell (APC) activation through engagement of CD40 by CD40 ligand on CD4+ T cells. To further study this three cell interaction, we established an in vitro system using dendritic cells (DCs) as APCs and influenza hemagglutinin (HA) class I and II peptide–specific T cell antigen receptor transgenic T cells as cytotoxic T lymphocyte precursors and CD4+ T helper cells, respectively. We found that CD4+ T cells can provide potent help for DCs to activate CD8+ T cells when antigen is provided in the form of either cell lysate, recombinant protein, or synthetic peptides. Surprisingly, this help is completely independent of CD40. Moreover, CD40-independent CD4+ help can be documented in vivo. Finally, we show that CD40-independent T cell help is delivered through both sensitization of DCs and direct CD4+–CD8+ T cell communication via lymphokines. Therefore, we conclude that CD4+ help comprises at least three components: CD40-dependent DC sensitization, CD40-independent DC sensitization, and direct lymphokine-dependent CD4+–CD8+ T cell communication.

scholarly journals Influenza virus hemagglutinin-specific cytotoxic T cell response induced by polypeptide produced in Escherichia coli.

1985 ◽  
Vol 162 (2) ◽  
pp. 663-674 ◽  
Author(s):  
A Yamada ◽  
M R Ziese ◽  
J F Young ◽  
Y K Yamada ◽  
F A Ennis
Keyword(s):  
Influenza Virus ◽  
Recombinant Dna ◽  
Cytotoxic T Lymphocyte ◽  
Nonstructural Protein ◽  
T Cell Response ◽  
Cytotoxic T Cell ◽  
Protein Immunization ◽  
Recombinant Dna Techniques

We have tested the abilities of various polypeptides of A/PR/8/34 (H1N1) virus, constructed by recombinant DNA techniques, to induce influenza virus-specific secondary cytotoxic T lymphocyte (CTL) responses. A hybrid protein (c13 protein), consisting of the first 81 amino acids of viral nonstructural protein (NS1) and the HA2 subunit of viral hemagglutinin (HA), induced H-2-restricted, influenza virus subtype-specific secondary CTL in vitro, although other peptides did not. Using a recombinant virus, the viral determinant responsible for recognition was mapped to the HA2 portion of c13 protein. Immunization of mice with c13 protein induced the generation of memory CTL in vivo. The CTL precursor frequencies of A/PR/8/34 virus- and c13 protein-immune mice were estimated as one in 8,047 and 50,312, respectively. These results indicate that c13 protein primed recipient mice, even though the level of precursor frequency was below that observed in virus-immune mice.

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 IMMUNOLOGIC REACTIONS TO HAPTENS ON AUTOLOGOUS CARRIERS

1973 ◽  
Vol 137 (2) ◽  
pp. 411-423 ◽  
Author(s):  
John W. Moorhead ◽  
Curla S. Walters ◽  
Henry N. Claman
Keyword(s):  
T Cells ◽  
B Cells ◽  
Aminocaproic Acid ◽  
Single Amino Acid ◽  
Secondary Response ◽  
Spleen Cells ◽  
Activated T Cells ◽  
Thymus Cells

Both thymus-derived (T) and bone marrow-derived (B) lymphocytes participate in the response to a hapten 4-hydroxy-3-iodo-5-nitrophenylacetic acid (NIP), coupled to a nonimmunogenic isologous carrier, mouse gamma globulin (MGG). Spleen cells from mice immunized with NIP-MGG show increased DNA synthesis in vitro when cultured with NIP-MGG. The participation of and requirement for T cells in the response was demonstrated by treating the spleen cells with anti-θ serum. This treatment resulted in a 77% inhibition of the antigen response. Furthermore, adoptively transferred normal thymus cells could be specifically "activated" by NIP-MGG in vivo and they responded secondarily to the antigen in vitro. The active participation of B cells in the secondary response was demonstrated by passing the immune spleen cells through a column coated with polyvalent anti-MGG serum. Column filtration reduced the number of NIP-specific plaque-forming cells and NIP-specific rosette-forming cells (both functions of B cells) and produced a 47% inhibition of the NIP-MGG response. The ability of the cells to respond to phytohemagglutinin (PHA) was not affected by column filtration showing that T cells were not being selectively removed. The participation of B cells in the in vitro NIP-MGG response was also shown by treatment of the spleen cells with antiserum specific for MGG and MGG determinants. B cells were removed by treatment with anti-IgM or polyvalent anti-MGG serum plus complement, resulting in a respective 46 and 49% inhibition of the response to NIP-MGG. (Treatment with anti-IgM serum had no effect on T cells.) The contribution of the hapten NIP to stimulation of T cells was investigated using NIP-MGG-activated thymus cells. These activated T cells responded in vitro very well to the NIP-MGG complex but not to the MGG carrier alone demonstrating the requirement of the hapten for T cell stimulation. The response was also partially inhibited (41%) by incubating the activated cells with NIP coupled to a single amino acid (epsilon-aminocaproic acid) before addition of NIP-MGG. These results demonstrated that T cells recognize the hapten NIP when it is coupled to the isologous carrier MGG.

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 Sequential responses of mouse spleen T cells in mixed lymphocyte culture-induced cytolysis.

1975 ◽  
Vol 141 (2) ◽  
pp. 508-512 ◽  
Author(s):  
P Häyry ◽  
L C Andersson
Keyword(s):  
T Cells ◽  
Mixed Lymphocyte Culture ◽  
Lymphocyte Culture ◽  
Mouse Spleen ◽  
Blast Transformation

T cells triggered to blast transformation and proliferation by histoincompatible cells have the capacity of reverting "back" to lymphocytes. These "secondary" lymphocytes and their progeny cells are able to respond repeatedly to the same allogeneic stimulus in vitro.

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