scholarly journals Differential HIV Epitope Processing in Monocytes and CD4 T Cells Affects Cytotoxic T Lymphocyte Recognition

2009 ◽  
Vol 200 (2) ◽  
pp. 236-243 ◽  
Author(s):  
Estibaliz Lazaro ◽  
Sasha Blue Godfrey ◽  
Pamela Stamegna ◽  
Tobi Ogbechie ◽  
Christopher Kerrigan ◽  
...  
Keyword(s):  
T Cells ◽  
T Lymphocyte ◽  
Cd4 T Cells ◽  
Cytotoxic T Lymphocyte

scholarly journals Induction of Cytotoxic T Lymphocyte Antigen 4 (Ctla-4) Restricts Clonal Expansion of Helper T Cells

2001 ◽  
Vol 194 (7) ◽  
pp. 893-902 ◽  
Author(s):  
Alden M. Doyle ◽  
Alan C. Mullen ◽  
Alejandro V. Villarino ◽  
Anne S. Hutchins ◽  
Frances A. High ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell Activation ◽  
T Lymphocyte ◽  
Cd4 T Cells ◽  
Cell Activation ◽  
Cytotoxic T Lymphocyte ◽  
Clonal Expansion ◽  
Negative Regulator ◽  
Lymphocyte Antigen ◽  
Cell Divisions

Cytotoxic T lymphocyte antigen (CTLA)-4 plays an essential role in immunologic homeostasis. How this negative regulator of T cell activation executes its functions has remained controversial. We now provide evidence that CTLA-4 mediates a cell-intrinsic counterbalance to restrict the clonal expansion of proliferating CD4+ T cells. The regulation of CTLA-4 expression and function ensures that, after ∼3 cell divisions of expansion, most progeny will succumb to either proliferative arrest or death over the ensuing three cell divisions. The quantitative precision of the counterbalance hinges on the graded, time-independent induction of CTLA-4 expression during the first three cell divisions. In contrast to the limits imposed on unpolarized cells, T helper type 1 (Th1) and Th2 effector progeny may be rescued from proliferative arrest by interleukin (IL)-12 and IL-4 signaling, respectively, allowing appropriately stimulated progeny to proceed to the stage of tissue homing. These results suggest that the cell-autonomous regulation of CTLA-4 induction may be a central checkpoint of clonal expansion of CD4+ T cells, allowing temporally and spatially restricted growth of progeny to be dictated by the nature of the threat posed to the host.

scholarly journals CD4+ T cells support cytotoxic T lymphocyte priming by controlling lymph node input

2011 ◽  
Vol 108 (21) ◽  
pp. 8749-8754 ◽  
Author(s):  
Y. Kumamoto ◽  
L. M. Mattei ◽  
S. Sellers ◽  
G. W. Payne ◽  
A. Iwasaki
Keyword(s):  
T Cells ◽  
Lymph Node ◽  
T Lymphocyte ◽  
Cd4 T Cells ◽  
Cytotoxic T Lymphocyte

scholarly journals Interleukin-12 is necessary for the priming of CD4+T cells required during the elicitation of HIV-1 gp120-specific cytotoxic T-lymphocyte function

Immunology ◽  
2008 ◽  
Vol 124 (4) ◽  
pp. 553-561 ◽  
Author(s):  
Shalini Gupta ◽  
Ramanamurthy Boppana ◽  
Gyan C. Mishra ◽  
Bhaskar Saha ◽  
Debashis Mitra
Keyword(s):  
T Cells ◽  
T Lymphocyte ◽  
Cd4 T Cells ◽  
Cytotoxic T Lymphocyte ◽  
Interleukin 12 ◽  
Lymphocyte Function ◽  
Hiv 1

HIV-specific cytotoxic T lymphocyte precursors exist in a CD28-CD8+ T cell subset and increase with loss of CD4 T cells

AIDS ◽  
1999 ◽  
Vol 13 (9) ◽  
pp. 1029-1033 ◽  
Author(s):  
Dorothy E. Lewis ◽  
Lixia Yang ◽  
Wei Luo ◽  
Xiao-ping Wang ◽  
John R. Rodgers
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocyte ◽  
Cd4 T Cells ◽  
Cytotoxic T Lymphocyte ◽  
Cell Subset ◽  
Cd8 T Cell ◽  
T Cell Subset

scholarly journals Immunologic Self-Tolerance Maintained by Cd25+Cd4+Regulatory T Cells Constitutively Expressing Cytotoxic T Lymphocyte–Associated Antigen 4

2000 ◽  
Vol 192 (2) ◽  
pp. 303-310 ◽  
Author(s):  
Takeshi Takahashi ◽  
Tomoyuki Tagami ◽  
Sayuri Yamazaki ◽  
Toshimitsu Uede ◽  
Jun Shimizu ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
T Lymphocyte ◽  
Cd4 T Cells ◽  
Cytotoxic T Lymphocyte ◽  
Costimulatory Molecule ◽  
Self Tolerance

This report shows that cytotoxic T lymphocyte–associated antigen 4 (CTLA-4) plays a key role in T cell–mediated dominant immunologic self-tolerance. In vivo blockade of CTLA-4 for a limited period in normal mice leads to spontaneous development of chronic organ-specific autoimmune diseases, which are immunopathologically similar to human counterparts. In normal naive mice, CTLA-4 is constitutively expressed on CD25+CD4+ T cells, which constitute 5–10% of peripheral CD4+ T cells. When the CD25+CD4+ T cells are stimulated via the T cell receptor in vitro, they potently suppress antigen-specific and polyclonal activation and proliferation of other T cells, including CTLA-4–deficient T cells, and blockade of CTLA-4 abrogates the suppression. CD28-deficient CD25+CD4+ T cells can also suppress normal T cells, indicating that CD28 is dispensable for activation of the regulatory T cells. Thus, the CD25+CD4+ regulatory T cell population engaged in dominant self-tolerance may require CTLA-4 but not CD28 as a costimulatory molecule for its functional activation. Furthermore, interference with this role of CTLA-4 suffices to elicit autoimmune disease in otherwise normal animals, presumably through affecting CD25+CD4+ T cell–mediated control of self-reactive T cells. This unique function of CTLA-4 could be exploited to potentiate T cell–mediated immunoregulation, and thereby to induce immunologic tolerance or to control autoimmunity.

scholarly journals Modulation of Susceptibility to HIV-1 Infection by the Cytotoxic T Lymphocyte Antigen 4 Costimulatory Molecule

1999 ◽  
Vol 191 (11) ◽  
pp. 1987-1998 ◽  
Author(s):  
James L. Riley ◽  
Katia Schlienger ◽  
Patrick J. Blair ◽  
Beatriz Carreno ◽  
Nancy Craighead ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocyte ◽  
Cd4 T Cells ◽  
Cytotoxic T Lymphocyte ◽  
Costimulatory Molecule ◽  
Lymphocyte Antigen ◽  
Viral Spread ◽  
Hiv 1

CD4 T cells activated in vitro by anti-CD3/28–coated beads are resistant to infection by CC chemokine receptor 5 (CCR5)-dependent HIV-1 isolates. In vivo, antigen-presenting cells (APCs) activate CD4 T cells in part by signaling through the T cell receptor and CD28, yet cells stimulated in this manner are susceptible to HIV-1 infection. We show that cytotoxic T lymphocyte antigen 4 (CTLA-4) engagement counteracts the CD28 antiviral effects, and that the ratio of CTLA-4 to CD28 engagement determines the susceptibility of HIV-1 infection. Furthermore, unopposed CTLA-4 signaling provided by CD28 blockade promotes vigorous HIV-1 replication, despite minimal T cell proliferation. Finally, CTLA-4 antibodies decrease the susceptibility of antigen-activated CD4 T cells to HIV, suggesting a potential approach to prevent or limit viral spread in HIV-1–infected individuals.

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