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 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.

Cytotoxic T lymphocytes and viral evolution in primary HIV-1 infection*

1999 ◽  
Vol 97 (6) ◽  
pp. 707-718 ◽  
Author(s):  
David A. PRICE ◽  
Chris A. O'CALLAGHAN ◽  
Joseph A. WHELAN ◽  
Philippa J. EASTERBROOK ◽  
Rodney E. PHILLIPS
Keyword(s):  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Viral Evolution ◽  
Case Series ◽  
Effector Cells ◽  
Lymphocyte Responses ◽  
Hiv 1

Efforts to develop immune-based therapies for HIV infection have been impeded by incomplete definition of the immunological correlates of protection. Despite many precedents demonstrating that CD8+ cytotoxic T lymphocytes are key mediators of protective anti-viral immunity in non-human animal models, direct evidence that these effector cells control viral replication in HIV-1 infection has remained elusive. The first part of this paper describes a detailed immunological and genetic study founded on evolutionary considerations. Following infection with HIV-1, virus variants which escaped recognition by autologous cytotoxic T lymphocytes were shown to possess a selection advantage within the host environment. Cytotoxic T lymphocytes therefore exert anti-viral pressure in vivo. This observation provides compelling evidence that cytotoxic T lymphocytes comprise a significant element of anti-retroviral immunity. Subsequently, the quantification of peripheral cytotoxic T lymphocyte frequencies utilizing peptide–(human leucocyte antigen class I) tetrameric complexes is described. Five patients with qualitatively similar immunodominant cytotoxic T lymphocyte responses during symptomatic primary HIV-1 infection were studied longitudinally. Expansions of virus-specific CD8+ lymphocytes comprising up to 2% of the total CD8+ T cell population were observed in the acute phase of infection. Antigenic load was identified as an important determinant of circulating HIV-1-specific CD8+ lymphocyte levels; however, significant numbers of such cells were also found to persist following prolonged therapeutic suppression of plasma viraemia. In addition, an analysis of antigenic sequence variation with time in this case series suggests that the early administration of combination anti-retroviral therapy may limit HIV-1 mutational escape from host cytolytic specificities. The implications of these preliminary data are discussed. The data presented suggest that vaccination protocols should aim to elicit vigorous cytotoxic T lymphocyte responses to HIV-1. Attempts to stimulate polyvalent responses to mutationally intolerant epitopes are likely to be most effective. Optimal management of HIV-1 infection requires an understanding of dynamic host–virus interactions, and may involve strategies designed to enhance cytotoxic T lymphocyte activity following periods of anti-retroviral drug therapy.

scholarly journals Induction of cytotoxic T lymphocytes against I-region-coded determinants: in vitro evidence for a third histocompatibility locus in the mouse.

1975 ◽  
Vol 142 (6) ◽  
pp. 1477-1487 ◽  
Author(s):  
H Wagner ◽  
D Götze ◽  
L Ptschelinzew ◽  
M Röllinghoff
Keyword(s):  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Mixed Lymphocyte Culture ◽  
Lymphocyte Culture ◽  
Blast Cells ◽  
Histocompatibility Locus ◽  
Ctl Induction

Determinants controlled by the I region of the murine H-2 complex provoked the generation of cytotoxic T lymphocytes (CTL) in both a secondary and primary mixed lymphocyte culture. The stimulating determinants appeared to be controlled by loci within the I-A subregion. The target antigens of the CTL generated were present on both lipopolysaccharide- and concanavalin-induced blast lymphocytes, but were barely detectable on phytohemagglutinin-induced blast cells. The stimulating capacity for CTL induction of a complete H-2 complex incompatibility by far exceeded the sum of H-2D/K-region and I-region incompatibility, respectively.

scholarly journals Gag-Positive Reservoir Cells Are Susceptible to HIV-Specific Cytotoxic T Lymphocyte Mediated Clearance In Vitro and Can Be Detected In Vivo

PLoS ONE ◽  
2013 ◽  
Vol 8 (8) ◽  
pp. e71879 ◽  
Author(s):  
Erin H. Graf ◽  
Matthew J. Pace ◽  
Bennett A. Peterson ◽  
Lindsay J. Lynch ◽  
Steve B. Chukwulebe ◽  
...  
Keyword(s):  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte

scholarly journals Heat Shock Protein–Peptide Complexes, Reconstituted In Vitro, Elicit Peptide-specific Cytotoxic T Lymphocyte Response and Tumor Immunity

1997 ◽  
Vol 186 (8) ◽  
pp. 1315-1322 ◽  
Author(s):  
Nathalie E. Blachere ◽  
Zihai Li ◽  
Rajiv Y. Chandawarkar ◽  
Ryuichiro Suto ◽  
Navdeep S. Jaikaria ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
T Lymphocyte ◽  
Synthetic Peptides ◽  
Cytotoxic T Lymphocyte ◽  
T Cell Response ◽  
Lymphocyte Response ◽  
Peptide Complexes

Heat shock protein (HSP) preparations derived from cancer cells and virus-infected cells have been shown previously to elicit cancer-specific or virus-specific immunity. The immunogenicity of HSP preparations has been attributed to peptides associated with the HSPs. The studies reported here demonstrate that immunogenic HSP–peptide complexes can also be reconstituted in vitro. The studies show that (a) complexes of hsp70 or gp96 HSP molecules with a variety of synthetic peptides can be generated in vitro; (b) the binding of HSPs with peptides is specific in that a number of other proteins tested do not bind synthetic peptides under the conditions in which gp96 molecules do; (c) HSP–peptide complexes reconstituted in vitro are immunologically active, as tested by their ability to elicit antitumor immunity and specific CD8+ cytolytic T lymphocyte response; and (d) synthetic peptides reconstituted in vitro with gp96 are capable of being taken up and re-presented by macrophage in the same manner as gp96– peptides complexes generated in vivo. These observations demonstrate that HSPs are CD8+ T cell response–eliciting adjuvants.

scholarly journals Anthrax Toxin-Mediated Delivery In Vivo and In Vitro of a Cytotoxic T-Lymphocyte Epitope from Ovalbumin

1998 ◽  
Vol 66 (2) ◽  
pp. 615-619 ◽  
Author(s):  
Jimmy D. Ballard ◽  
Amy M. Doling ◽  
Kathryn Beauregard ◽  
R. John Collier ◽  
Michael N. Starnbach
Keyword(s):  
Fusion Protein ◽  
T Lymphocyte ◽  
Self Assembly ◽  
Protective Antigen ◽  
Cytotoxic T Lymphocyte ◽  
Ex Vivo ◽  
Lethal Factor ◽  
Anthrax Toxin

ABSTRACT We reported earlier that a nontoxic form of anthrax toxin was capable of delivering a cytotoxic T-lymphocyte (CTL) epitope in vivo, such that a specific CTL response was primed against the epitope. The epitope, of bacterial origin, was fused to an N-terminal fragment (LFn) from the lethal-factor component of the toxin, and the fusion protein was injected, together with the protective antigen (PA) component, into BALB/c mice. Here we report that PA plus LFn is capable of delivering a different epitope—OVA257–264 from ovalbumin. Delivery was accomplished in a different mouse haplotype,H-2Kb and occurred in vitro as well as in vivo. An OVA257–264-specific CTL clone, GA-4, recognized EL-4 cells treated in vitro with PA plus as little as 30 fmol of the LFn-OVA257–264 fusion protein. PA mutants attenuated in toxin self-assembly or translocation were inactive, implying that the role of PA in epitope delivery is the same as that in toxin action. Also, we showed that OVA257–264-specific CTL could be induced to proliferate by incubation with splenocytes treated with PA plus LFn-OVA257–264. These findings imply that PA-LFn may serve as a general delivery vehicle for CTL epitopes in vivo and as a safe, efficient tool for the ex vivo expansion of patient-derived CTL for use in adoptive immunotherapy.

scholarly journals Use of a High-Affinity Peptide That Aborts MHC-Restricted Cytotoxic T Lymphocyte Activity against Multiple Viruses in Vitro and Virus-Induced Immunopathologic Disease in Vivo

Virology ◽  
1999 ◽  
Vol 256 (2) ◽  
pp. 246-257 ◽  
Author(s):  
Michael B.A. Oldstone ◽  
Matthias von Herrath ◽  
Hanna Lewicki ◽  
Denis Hudrisier ◽  
J.Lindsay Whitton ◽  
...  
Keyword(s):  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
High Affinity ◽  
Lymphocyte Activity ◽  
Affinity Peptide
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