scholarly journals Allorestricted cytotoxic T cells. Large numbers of allo-H-2Kb-restricted antihapten and antiviral cytotoxic T cell populations clonally develop in vitro from murine splenic precursor T cells.

1985 ◽  
Vol 162 (2) ◽  
pp. 592-606 ◽  
Author(s):  
J Reimann ◽  
D Kabelitz ◽  
K Heeg ◽  
H Wagner
Keyword(s):  
T Cells ◽  
High Probability ◽  
Cytotoxic T Lymphocyte ◽  
Cytotoxic T Cells ◽  
Large Fraction ◽  
Cytotoxic T Cell ◽  
Wild Type ◽  
Large Numbers ◽  
Simplex Virus

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.

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 Delayed Clearance of Ehrlichia chaffeensis Infection in CD4+ T-Cell Knockout Mice†

2004 ◽  
Vol 72 (1) ◽  
pp. 159-167 ◽  
Author(s):  
Roman R. Ganta ◽  
Chuanmin Cheng ◽  
Melinda J. Wilkerson ◽  
Stephen K. Chapes
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cytotoxic T Cells ◽  
Cell Activity ◽  
Helper T Cells ◽  
Cytotoxic T Cell ◽  
Mouse Strains ◽  
Cell Mediated Immunity ◽  
Ehrlichia Chaffeensis ◽  
Wild Type

ABSTRACT Human monocytic ehrlichiosis is an emerging tick-borne disease caused by the rickettsia Ehrlichia chaffeensis. To examine the role of helper T cells in host resistance to this macrophage-tropic bacterium, we assessed E. chaffeensis infections in three mouse strains with differing functional levels of helper T cells. Wild-type, C57BL/6J mice resolved infections in approximately 2 weeks. Major histocompatibility complex class II (MHCII) knockout, B6.129-Abb tm1 mice lacking helper T cells developed persistent infections that were not resolved even after several months. CD4+ T-cell-deficient, B6.129S6-Cd4 tm1Knw mice cleared the infection, but the clearance took 2 weeks longer than it did for wild-type mice. C57BL/6J mice resolved infection more rapidly following a second experimental challenge, but B6.129S6-Cd4 tm1Knw mice did not. The B6.129S6-Cd4 tm1Knw mice also developed active E. chaffeensis-specific immunoglobulin G responses that were slightly lower in concentration and slower to develop than that observed in C57BL/6J mice. E. chaffeensis-specific cytotoxic T cells were not detected following a single bacterial challenge in any mouse strain, including wild-type C57BL/6J mice. However, the cytotoxic T-cell activity developed in all three mouse strains, including the MHCII and CD4+ T-cell knockouts, when challenged with a second E. chaffeensis infection. The data reported here suggest that the cell-mediated immunity, orchestrated by CD4+ T cells is critical for conferring rapid clearance of E. chaffeensis.

scholarly journals Role of viral infectivity in the induction of influenza virus-specific cytotoxic T cells.

1978 ◽  
Vol 147 (4) ◽  
pp. 1236-1252 ◽  
Author(s):  
T J Braciale ◽  
K L Yap
Keyword(s):  
T Cells ◽  
Influenza Virus ◽  
T Cell ◽  
Cell Response ◽  
Infectious Virus ◽  
Cytotoxic T Cells ◽  
T Cell Response ◽  
Cytotoxic T Cell

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.

scholarly journals Specificity of cytotoxicity T cells directed to influenza virus hemagglutinin.

1979 ◽  
Vol 149 (4) ◽  
pp. 856-869 ◽  
Author(s):  
T J Braciale
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cytotoxic T Cells ◽  
Type A ◽  
Cross Reactivity ◽  
Cytotoxic T Cell ◽  
Target Cells ◽  
Effector Cells ◽  
Cell Induction

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.

scholarly journals In vitro generation of antigen-specific helper T cells that collaborate with cytotoxic T-cell precursors.

1978 ◽  
Vol 148 (6) ◽  
pp. 1579-1591 ◽  
Author(s):  
L L Baum ◽  
L M Pilarski
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cytotoxic T Cells ◽  
Cell Activity ◽  
Helper T Cells ◽  
Helper Cell ◽  
Cytotoxic T Cell ◽  
Spleen Cells

Antigen-specific helper T cells are required in the generation of cytotoxic T cells from thymocyte precursors. We have demonstrated that these alloantigen-specific helper cells can be generated in vitro and that both the quantity and quality of the helpers appear to be superior to the help obtained from unprimed spleen cells. Optimal helper cell activity is produced at day two of culture when CBA splenic helper precursors are stimulated by irradiated allogeneic spleen cells. Helper cell precursors are antigen-specific cells which cannot be instructed to express forbidden receptor specificities and bear theta antigen on their surface. The helper effectors are radioresistant, theta-bearing, and antigen-specific cells.

scholarly journals Cd8− T Cell Transfectants That Express a High Affinity T Cell Receptor Exhibit Enhanced Peptide-Dependent Activation

2001 ◽  
Vol 194 (8) ◽  
pp. 1043-1052 ◽  
Author(s):  
Phillip D. Holler ◽  
Alice R. Lim ◽  
Bryan K. Cho ◽  
Laurie A. Rund ◽  
David M. Kranz
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Cytotoxic T Lymphocyte ◽  
Cell Activity ◽  
Cell Receptor ◽  
Wild Type ◽  
High Affinity ◽  
Antigen Presenting

T cells are activated by binding of the T cell receptor (TCR) to a peptide-major histocompatibility complex (MHC) complex (pMHC) expressed on the surface of antigen presenting cells. Various models have predicted that activation is limited to a narrow window of affinities (or dissociation rates) for the TCR–pMHC interaction and that above or below this window, T cells will fail to undergo activation. However, to date there have not been TCRs with sufficiently high affinities in order to test this hypothesis. In this report we examined the activity of a CD8-negative T cell line transfected with a high affinity mutant TCR (KD = 10 nM) derived from cytotoxic T lymphocyte clone 2C by in vitro engineering. The results show that despite a 300-fold higher affinity and a 45-fold longer off-rate compared with the wild-type TCR, T cells that expressed the mutant TCRs were activated by peptide. In fact, activation could be detected at significantly lower peptide concentrations than with T cells that expressed the wild-type TCR. Furthermore, binding and functional analyses of a panel of peptide variants suggested that pMHC stability could account for apparent discrepancies between TCR affinity and T cell activity observed in several prior studies.

scholarly journals Cd8+ but Not Cd8− Dendritic Cells Cross-Prime Cytotoxic T Cells in Vivo

2000 ◽  
Vol 192 (12) ◽  
pp. 1685-1696 ◽  
Author(s):  
Joke M.M. den Haan ◽  
Sophie M. Lehar ◽  
Michael J. Bevan
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Mhc Class I ◽  
Cytotoxic T Lymphocyte ◽  
Cytotoxic T Cells ◽  
Class I ◽  
Specific Subset ◽  
Mhc Class I Molecules

Bone marrow–derived antigen-presenting cells (APCs) take up cell-associated antigens and present them in the context of major histocompatibility complex (MHC) class I molecules to CD8+ T cells in a process referred to as cross-priming. Cross-priming is essential for the induction of CD8+ T cell responses directed towards antigens not expressed in professional APCs. Although in vitro experiments have shown that dendritic cells (DCs) and macrophages are capable of presenting exogenous antigens in association with MHC class I, the cross-presenting cell in vivo has not been identified. We have isolated splenic DCs after in vivo priming with ovalbumin-loaded β2-microglobulin–deficient splenocytes and show that they indeed present cell-associated antigens in the context of MHC class I molecules. This process is transporter associated with antigen presentation (TAP) dependent, suggesting an endosome to cytosol transport. To determine whether a specific subset of splenic DCs is involved in this cross-presentation, we negatively and positively selected for CD8− and CD8+ DCs. Only the CD8+, and not the CD8−, DC subset demonstrates cross-priming ability. FACS® studies after injection of splenocytes loaded with fluorescent beads showed that 1 and 0.6% of the CD8+ and the CD8− DC subsets, respectively, had one or more associated beads. These results indicate that CD8+ DCs play an important role in the generation of cytotoxic T lymphocyte responses specific for cell-associated antigens.

scholarly journals The interaction between CD8+ cytotoxic T cells and Leishmania-infected macrophages.

1991 ◽  
Vol 174 (3) ◽  
pp. 499-505 ◽  
Author(s):  
L E Smith ◽  
M Rodrigues ◽  
D G Russell
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Clone ◽  
Cytotoxic T Cells ◽  
T Cell Response ◽  
Cytotoxic T Cell ◽  
T Cell Clone ◽  
Vitro Model ◽  
Leishmania Parasites

Leishmania is resident within the macrophages of its vertebrate host. In any intramacrophage infection, where the pathogen is present in a form capable of mediating cell to cell transmission, the contribution of a cytotoxic T cell response to protective immunity is questionable. This study presents data from an in vitro model designed to elucidate the outcome of an interaction between CD8+, cytotoxic T cells and infected macrophages. Experiments were conducted with an H-2d-restricted, cytotoxic CD8+ T cell clone and Leishmania parasites present in mixed macrophage cultures, with the parasites confined to either histocompatible BALB/c macrophages, or incompatible CBA macrophages. Initial experiments indicated that the viability of Leishmania was unaffected by the lysis of its host macrophage by cytotoxic T cells. However, extended experiments showed that the parasites were killed between 24 and 72 h. The same results were obtained regardless of whether the parasites were resident in the target, BALB/c, macrophages or the bystander, CBA, macrophages. Addition of neutralizing, anti-IFN-g antibody to the cultures ablated most of the leishmanicidal behavior, indicating that parasite death was attributable to macrophage activation, resulting from cytokine secretion from the T cells following the initial recognition event.

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
Keyword(s):  
T Cells ◽  
Monoclonal Antibodies ◽  
T Helper Cells ◽  
Cytotoxic T Cells ◽  
T Helper Cell ◽  
Cytotoxic T Cell ◽  
T Helper ◽  
Cell Induction ◽  
D Region

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.

Helminths' antigens differentially modulate the activation of SARS-CoV-2-reactive helper and cytotoxic T cells in COVID-19 patients and healthy blood donors

2021 ◽  
Author(s):  
Tomabu Adjobimey ◽  
Julia Meyer ◽  
Vedrana Terkeš ◽  
Marijo Parcina ◽  
Achim Hoerauf
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cytotoxic T Cells ◽  
Sub Saharan Africa ◽  
Cytotoxic T Cell ◽  
Immune Reactivity ◽  
Sub Saharan ◽  
Cytotoxic T Cell Responses ◽  
The Impact

Abstract Background Contrary to the predictions, prevalence and mortality due to COVID-19 have remained moderate on the African continent. Several factors, including age, genetics, vaccines, and co-infections, might impact the course of the pandemic in Africa. Helminths are highly endemic in Sub-Saharan Africa and are renowned for their ability to modulate their host immune reactions. Methods Here we analyzed in vitro the impact of major helminth antigens on the immune reactivity to SARS-CoV-2 in COVID-19 patients using flow cytometry and Luminex. Results: We observed that helminth antigens significantly reduced the frequency of SARS-CoV-2-reactive CD4+ T helper cells. In contrast, the expression of SARS-CoV-2-reactive CD8+ T cells was not affected. In addition, stimulation with helminth antigens was associated with increased IL-10 and a reduction of IFNγ and TNFα. Conclusion: Our data offer a plausible explanation for the moderate incidence of COVID-19 in Africa and support the hypothesis that helper T cell-mediated immune responses to SARS-CoV-2 are mitigated in the presence of helminth antigens, while virus-specific cytotoxic T cell responses are maintained.

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