scholarly journals Analysis of the cytotoxic T-lymphocyte-associated protein 4 (Ctla4)-dependent transcriptome in murine effector CD4+ T lymphocytes (T-cells) in a physiological model of immunity to foreign antigen

Author(s):  
E Corse
1987 ◽  
Vol 166 (5) ◽  
pp. 1536-1547 ◽  
Author(s):  
C R Verret ◽  
A A Firmenich ◽  
D M Kranz ◽  
H N Eisen

A cytotoxic T lymphocyte (CTL) characteristically kills target cells one after the other by releasing toxic granules that contain one or more cytolytic components. To determine how CTLs avoid destroying themselves when they release granules and lyse target cells, 7 murine CD8+ CTL cell lines were compared with 19 other cell lines for susceptibility to lysis by the isolated toxic granules. Murine CD8+ CTLs were clearly the most resistant cells: granules did not lyse them even after they were exposed to azide, cyanide, and 2-deoxyglucose, conditions that were found to enhance the susceptibility of all the other cells tested, including other T cells. Thus, resistance of CD8+ CTLs to cytotoxic granules appears to be independent of cellular ATP. To reconcile these findings with other observations that, under some circumstances, CTLs can be lysed by other CTLs, we suggest a model in which a CTL releases only a limited proportion of its toxic granules at each antigen-specific encounter with a target cell; the amount released is sufficient to kill most target cells but to leave the CTL undamaged and with enough granules to attack other target cells.


1998 ◽  
Vol 187 (3) ◽  
pp. 427-432 ◽  
Author(s):  
Fred Lühder ◽  
Petter Höglund ◽  
James P. Allison ◽  
Christophe Benoist ◽  
Diane Mathis

Evidence has been accumulating that shows that insulin-dependent diabetes is subject to immunoregulation. To determine whether cytotoxic T lymphocyte–associated antigen 4 (CTLA-4) is involved, we injected anti–CTLA-4 mAb into a TCR transgenic model of diabetes at different stages of disease. When injected into young mice, months before they would normally become diabetic, anti–CTLA-4 induced diabetes rapidly and essentially universally; this was not the result of a global activation of T lymphocytes, but did reflect a much more aggressive T cell infiltrate in the pancreatic islets. These effects were only observed if anti–CTLA-4 was injected during a narrow time window, before the initiation of insulitis. Thus, engagement of CTLA-4 at the time when potentially diabetogenic T cells are first activated is a pivotal event; if engagement is permitted, invasion of the islets occurs, but remains quite innocuous for months, if not, insulitis is much more aggressive, and diabetes quickly ensues.


2000 ◽  
Vol 74 (18) ◽  
pp. 8299-8306 ◽  
Author(s):  
Patric Lundberg ◽  
Gary A. Splitter

ABSTRACT Bovine leukemia virus (BLV) is a complex B-lymphotrophic retrovirus of cattle and the causative agent of enzootic bovine leukosis. Serum antibody in infected animals does not correlate with protection from disease, yet only some animals develop severe disease. While a cytotoxic T-lymphocyte response may be responsible for directing BLV pathogenesis, this possibility has been left largely unexplored, in part since the lack of readily established cytotoxic target cells in cattle has hampered such studies. Using long-term naturally infected alymphocytic (AL) cattle, we have established the existence of cytotoxic T-lymphocyte response against BLV envelope proteins (Env; gp51/gp30). In vitro-expanded peripheral blood mononuclear (PBM) cell effector populations consisted mainly of γδ+ (>40%), CD4+ (>35%), and CD8+ (>10%) T lymphocytes. Specific lysis of autologous fibroblasts infected with recombinant vaccinia virus (rVV) delivering the BLV env gene ranged from 30 to 65%. Depletion studies indicated that γδ+ and not CD8+ T cells were responsible for the cytotoxicity against autologous rVVenv-expressing fibroblasts. Additionally, cultured effector cells lysed rVVenv-expressing autologous fibroblasts and rVVenv-expressing xenogeneic targets similarly, suggesting a lack of genetic restricted killing. Restimulation of effector populations increased the proportion of γδ+ T cells and concomitantly Env-specific cytolysis. Interestingly, culture of cells from BLV-negative or persistently lymphocytic cattle failed to elicit such cytotoxic responses or increase in γδ+ T-cell numbers. These results imply that cytotoxic γδ+ T lymphocytes from only AL cattle recognize BLV Env without a requirement for classical major histocompatibility complex interactions. It is known that γδ+ T lymphocytes are diverse and numerous in cattle, and here we show that they may serve a surveillance role during natural BLV infection.


2011 ◽  
Vol 19 (1) ◽  
pp. 45-52 ◽  
Author(s):  
Alexandre S. de Almeida ◽  
Christina T. Fiske ◽  
Timothy R. Sterling ◽  
Spyros A. Kalams

ABSTRACTExtrapulmonary tuberculosis may be due to underlying immune compromise. Immunosuppressive regulatory T cells (Treg cells), and CD4+T lymphocytes in general, are important in the host immune response toMycobacterium tuberculosis. We evaluated T lymphocytes from patients after recovery from extrapulmonary tuberculosis, which may reflect conditions beforeM. tuberculosisinfection. A case-control study was conducted among HIV-uninfected adults with previously treated extrapulmonary tuberculosis and 3 sets of controls: (i) subjects with previously treated pulmonary tuberculosis, (ii) close tuberculosis contacts withM. tuberculosisinfection, and (iii) close tuberculosis contacts with no infection. Monocyte-depleted peripheral blood mononuclear cells (PBMC-M) were stained for CD4+CD25hiCD127lowFoxP3+cell (Treg cell) and T lymphocyte activation. Both characteristics were compared as continuous variables between groups with the Kruskal-Wallis test. There were 7 extrapulmonary tuberculosis cases, 18 pulmonary tuberculosis controls, 17 controls withM. tuberculosisinfection, and 18 controls withoutM. tuberculosisinfection. The median Treg cell proportion was highest among persons with previous extrapulmonary tuberculosis (1.23%) compared to subjects with pulmonary tuberculosis (0.56%), latentM. tuberculosisinfection (0.14%), or noM. tuberculosisinfection (0.20%) (P= 0.001). The median proportion of CD4+T lymphocytes that expressed the activation markers HLA-DR and CD38 was highest for CD4+T lymphocytes from persons with previous extrapulmonary tuberculosis (0.79%) compared to subjects with pulmonary tuberculosis (0.44%), latentM. tuberculosisinfection (0.14%), or noM. tuberculosisinfection (0.32%) (P= 0.005). Compared with controls, persons with previously treated extrapulmonary tuberculosis had the highest Treg cell frequency, but also the highest levels of CD4+T lymphocyte activation. Immune dysregulation may be a feature of individuals at risk for extrapulmonary tuberculosis.


2009 ◽  
Vol 200 (2) ◽  
pp. 236-243 ◽  
Author(s):  
Estibaliz Lazaro ◽  
Sasha Blue Godfrey ◽  
Pamela Stamegna ◽  
Tobi Ogbechie ◽  
Christopher Kerrigan ◽  
...  

1997 ◽  
Vol 13 (1) ◽  
pp. 33-39 ◽  
Author(s):  
MARC DUPUIS ◽  
MADHUSUDAN V. PESHWA ◽  
CLAUDIA BENIKE ◽  
SMRITI K. KUNDU ◽  
EDGAR G. ENGLEMAN ◽  
...  

2011 ◽  
Vol 129 (5) ◽  
pp. 1126-1136 ◽  
Author(s):  
Masaaki Toda ◽  
Linan Wang ◽  
Suguru Ogura ◽  
Mie Torii ◽  
Makoto Kurachi ◽  
...  

2000 ◽  
Vol 355 (1395) ◽  
pp. 361-362 ◽  
Author(s):  
Peter C. Doherty

The school of thought that owes allegiance to Ludwig Wittgenstein teaches that language conditions perceptions. When we use the term ‘cytotoxic T lymphocyte’ or ‘helper Tcell’ we tend to orientate our own thinking processes, and those of listeners or readers, down particular paths. Part of the problem is that we are often describing cell populations by functions that may either be a property of only a proportion of those that are being assayed, or are simply inferred from the expression of various cell–surface markers. The consequence can be a measure of confusion that might be avoided if we could communicate with greater clarity. Is it possible to achieve a better terminology that will be accepted generally? The following are some examples of why there may be some value in thinking about this.


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