scholarly journals Analysis of H-2 determinants recognized during the induction of H-Y-immune cytotoxic T cells by monoclonal antibodies in vitro

1981 ◽  
Vol 154 (2) ◽  
pp. 563-568 ◽  
Author(s):  
M Brenan ◽  
A Mullbacher

Monoclonal antibodies directed to the D region of H-2(k) when present during in vitro culture inhibit the generation of CBA/H and C3H.H-2(o) H-Y-immune cytotoxic T cells . Monoclonal antibodies directed to the I-A(k) and I-E(k) region specifically inhibited induction of CBA/H H-Y-immune cytotoxic T cells only when they were present simultaneously in culture. These findings show T helper cell requirement for CBA/H H-Y-immune cytotoxic T cell induction, and suggest that two I region-coded restriction antigens for T helper cells are involved.

1979 ◽  
Vol 150 (5) ◽  
pp. 1277-1282 ◽  
Author(s):  
R B Ashman ◽  
A Müllbacher

We demonstrate here: (a) the existence of T helper (Th) cells that augment the generation of virus-specific cytotoxic T cells in vitro, (b) that the helper cells carry the theta and Ly 1 membrane antigens, (c) that activation of the Th effect is specific for viral antigens, and (d) that the delivery of help is not H-2 restricted.


2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Michaela Gasch ◽  
Tina Goroll ◽  
Mario Bauer ◽  
Denise Hinz ◽  
Nicole Schütze ◽  
...  

The T helper cell subsets Th1, Th2, Th17, and Treg play an important role in immune cell homeostasis, in host defense, and in immunological disorders. Recently, much attention has been paid to Th17 cells which seem to play an important role in the early phase of the adoptive immune response and autoimmune disease. When generating Th17 cells underin vitroconditions the amount of IL-17A producing cells hardly exceeds 20% while the nature of the remaining T cells is poorly characterized. As engagement of the aryl hydrocarbon receptor (AHR) has also been postulated to modulate the differentiation of T helper cells into Th17 cells with regard to the IL-17A expression we ask how far do Th17 polarizing conditions in combination with ligand induced AHR activation have an effect on the production of other T helper cell cytokines. We found that a high proportion of T helper cells cultured under Th17 polarizing conditions are IL-8 and IL-9 single producing cells and that AHR activation results in an upregulation of IL-8 and a downregulation of IL-9 production. Thus, we have identified IL-8 and IL-9 producing T helper cells which are subject to regulation by the engagement of the AHR.


1979 ◽  
Vol 149 (4) ◽  
pp. 856-869 ◽  
Author(s):  
T J Braciale

Purified type A influenza viral hemagglutinin stimulates an in vitro cell-mediated cytotoxic cell response that exhibits a high degree of specificity for the immunizing hemagglutinin. The response magnitude is proportional to the hemagglutinin dose used for stimulation. The lytic activity of the effector cells is H-2 restricted. Analysis of the specificity of the response indicated that these cytotoxic T cells readily distinguish target cells expressing serologically unrelated hemagglutinin from target cells bearing hemagglutinins serologically related to the stimulating hemagglutinin. Further analysis of the fine specificity of cytotoxic T-cell recognition with serologically cross-reactive type A influenza hemagglutinins revealed a hierarchy of cross-reactivity among these hemagglutinins that was the converse of the serologic hierarchy. These results are discussed in terms of possible differences and similarities in the specificity repertoire of cytotoxic T cells and antibodies. Possible implications of these findings from the standpoint of cytotoxic T-cell induction are also discussed.


1980 ◽  
Vol 151 (1) ◽  
pp. 133-143 ◽  
Author(s):  
J J Jandinski ◽  
J Li ◽  
P J Wettstein ◽  
J A Frelinger ◽  
D W Scott

Trinitrophenylated syngeneic spleen cells (TNP-SC) are potent tolerogens of the anti-TNP plaque-forming cell (PFC) response in vivo and in vitro. This unresponsive state requires T cells for both its induction and maintenance. Because H-2K/D-restricted cytotoxic T cells are also induced by exposure to TNP-SC, we determined the role(s) of histocompatibility antigens (K, I, and D) in the suppression of the PFC response by TNP-SC. We treated syngeneic TNP-modified stimulator cells with antiserum directed at K-, I-, or D-region determinants and found that blocking of H-2K or D antigens on TNP-SC transformed these tolerogens into immunogens capable of eliciting an anti-TNP PFC response in the absence of extrinsic immunogens like TNP-polymerized flagellin. In H-2k or H-2a(k/d) mice, only H-2Kk needs to be blocked on the stimulator cells, whereas H-2K or D recognition was apparent in B10.A(4R) mice. These observations indicate that suppression of the PFC response by TNP-SC shows the same restriction in recognition as does the cytotoxic T-cell response. Furthermore, our results suggest that TNP-I-A is recognized by the helper cells in this system as the intrinsic antigen. When both TNP-K and TNP-I-A are present and available on the same stimulator cell, suppression (via modified K recognition) is dominant over help.


2003 ◽  
Vol 12 (5) ◽  
pp. 285-292 ◽  
Author(s):  
Scott B. Cameron ◽  
Ellen H. Stolte ◽  
Anthony W. Chow ◽  
Huub F. J. Savelkoul

Background:T helper cell polarisation is important under chronic immune stimulatory conditions and drives the type of the evolving immune response. Mice treated with superantigensin vivodisplay strong effects on Thsubset differentiation. The aim of the study was to detect the intrinsic capacity of T cells to polarise under variousex vivoconditions.Methods:Purified CD4+T cells obtained from superantigen-treated mice were cultured under Thpolarising conditionsin vitro. By combining intracellular cytokine staining and subsequent flow cytometric analysis with quantitative cytokine measurements in culture supernatants by enzyme-linked immunosorbent assay (ELISA), the differential Thpolarising capacity of the treatment can be detected in a qualitative and quantitative manner.Results and conclusions:BALB/c mice were shown to be biased to develop strong Th2 polarised immune responses using Th0 stimulation of purified CD4+T cells from phosphate-buffered saline-treated mice. Nevertheless, our analysis methodology convincingly showed that even in these mice, Toxic Shock Syndrome Toxin-1 treatmentin vivoresulted in a significantly stronger Th1 polarising effect than control treatment. Our results indicate that populations of Thcells can be assessed individually for their differential Th1 or Th2 maturation capacityin vivoby analysing robustin vitropolarisation cultures combined with intracellular cytokine staining and ELISA.


1998 ◽  
Vol 187 (7) ◽  
pp. 1151-1156 ◽  
Author(s):  
Yan Wu ◽  
Qunmin Zhou ◽  
Pan Zheng ◽  
Yang Liu

It is well established that B7-CD28/CTLA4 interactions play an important role in the induction of T helper cells for T-dependent antibody responses. However, targeted mutation of CD28 does not significantly affect production of IgG and activation of CD4 T helper cells in response to infections by some viruses and nematode parasites. To test whether the CD28-independent induction of Ig class switches requires costimulation by the heat-stable antigen (HSA), we compared T helper cell induction and antibody response in mice deficient for either HSA, CD28, or both genes. We found that after immunization with KLH-DNP, mice deficient for both CD28 and HSA lack DNP-specific IgA and all subtypes of IgG. This deficiency corresponds to a reduced number of effector helper T cells that rapidly produce IL-2, IL-4, and IFN-γ after in vitro stimulation with carrier antigen KLH. In contrast, priming of T helper cells and Ig class switch are normal in mice deficient with either HSA or CD28 alone. IgM responses are not affected by any of these targeted mutations. These results demonstrate that CD28-independent induction of T helper cells and Ig class-switches requires costimulation by the HSA.


1985 ◽  
Vol 162 (2) ◽  
pp. 592-606 ◽  
Author(s):  
J Reimann ◽  
D Kabelitz ◽  
K Heeg ◽  
H Wagner

Cytotoxic T lymphocyte (CTL) responses of splenic T cells from C57BL/6 B6) mice and mutant H-2Kbm1 (bm1) mice to haptenic (trinitrophenyl [TNP] ) and herpes simplex virus (HSV) determinants in the context of an allogenic (wild-type or mutant) H-2Kb molecule were analyzed in a modified limiting dilution system. In the B6-anti-bm1TNP mixed leukocyte reaction (MLR), estimated frequencies for precursors of CTL clones that lysed bm1TNP targets ranged from 1/120 to 1/400; in the bm1-anti-B6TNP MLR, estimated frequencies of precursors of CTL clones that lysed B6TNP targets ranged from 1/500 to 1/1,300. Estimated frequencies for precursors of CTL clones that lysed the respective unmodified and TNP-modified allogeneic targets were two- to three-fold lower. Lytic specificity patterns determined by split-well analysis showed that at least 20-30% of the generated CTL populations (selected for a high probability of clonality) in both MLR displayed allorestricted lysis of TNP-modified concanavalin A blast targets. In the B6-anti-bm1HSV MLR, estimated frequencies for precursors of CTL clones that lysed bm1HSV targets ranged from 1/70 to 1/300; in the bm1-anti-B6HSV MLR, estimated frequencies for precursors of CTL clones that lysed B6HSV targets ranged from 1/300 to 1/1,200. Again, estimated frequencies for precursors of CTL clones that lysed the respective noninfected and virus-infected allogeneic targets were two- to fourfold lower. Of the CTL populations selected for a high probability of clonality at least 30-60% displayed allorestricted lysis of virus-infected lipopolysaccharide blast targets in both MLR. It is concluded that a large fraction of clonally developing CTL populations stimulated with TNP-modified or HSV-infected allo-H-2Kb-bearing cells displayed an allorestricted pattern of recognition. It was further evident that the estimated frequencies of splenic precursors that generated allorestricted CTL clones was two- to threefold higher than the estimated frequencies of precursors that gave rise to the respective alloreactive CTL populations.


1978 ◽  
Vol 147 (4) ◽  
pp. 1236-1252 ◽  
Author(s):  
T J Braciale ◽  
K L Yap

This report examines the requirement for infectious virus in the induction of influenza virus-specific cytotoxic T cells. Infectious influenza virus was found to be highly efficient at generating both primary and secondary cytotoxic T-cell response in vivo. Inactivated influenza virus however, failed to stimulate a detectable cytotoxic T-cell response in vivo even at immunizing doses 10(5)-10(6)-fold higher than the minimum stimulatory dose of infectious virus. Likewise inactivated virus failed to sensitize target cells for T cell-mediated lysis in vitro but could stimulate a specific cytotoxic response from primed cells in vitro. Possible requirements for the induction of virus-specific cytotoxic T-cell responses are discussed in light of these observations and those of other investigators.


2003 ◽  
Vol 198 (2) ◽  
pp. 259-266 ◽  
Author(s):  
Guillaume Oldenhove ◽  
Magali de Heusch ◽  
Georgette Urbain-Vansanten ◽  
Jacques Urbain ◽  
Charlie Maliszewski ◽  
...  

Recent evidence suggests that in addition to their well known stimulatory properties, dendritic cells (DCs) may play a major role in peripheral tolerance. It is still unclear whether a distinct subtype or activation status of DC exists that promotes the differentiation of suppressor rather than effector T cells from naive precursors. In this work, we tested whether the naturally occurring CD4+ CD25+ regulatory T cells (Treg) may control immune responses induced by DCs in vivo. We characterized the immune response induced by adoptive transfer of antigen-pulsed mature DCs into mice depleted or not of CD25+ cells. We found that the development of major histocompatibility complex class I and II–restricted interferon γ–producing cells was consistently enhanced in the absence of Treg. By contrast, T helper cell (Th)2 priming was down-regulated in the same conditions. This regulation was independent of interleukin 10 production by DCs. Of note, splenic DCs incubated in vitro with Toll-like receptor ligands (lipopolysaccharide or CpG) activated immune responses that remained sensitive to Treg function. Our data further show that mature DCs induced higher cytotoxic activity in CD25-depleted recipients as compared with untreated hosts. We conclude that Treg naturally exert a negative feedback mechanism on Th1-type responses induced by mature DCs in vivo.


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