scholarly journals Differential requirements of CD4+T-cell signals for effector cytotoxic T-lymphocyte (CTL) priming and functional memory CTL development at higher CD8+T-cell precursor frequency

Immunology ◽  
2013 ◽  
Vol 138 (4) ◽  
pp. 298-306 ◽  
Author(s):  
Channakeshava S. Umeshappa ◽  
Roopa H. Nanjundappa ◽  
Yufeng Xie ◽  
Andrew Freywald ◽  
Qingyong Xu ◽  
...  
Keyword(s):  
T Cell ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Cd8 T Cell ◽  
Cd4 T Cell ◽  
Cell Precursor ◽  
Precursor Frequency ◽  
Cell Signals

scholarly journals CD4+ T cell-released exosomes inhibit CD8+ cytotoxic T-lymphocyte responses and antitumor immunity

2010 ◽  
Vol 8 (1) ◽  
pp. 23-30 ◽  
Author(s):  
Haifeng Zhang ◽  
Yufeng Xie ◽  
Wei Li ◽  
Rajni Chibbar ◽  
Sidong Xiong ◽  
...  
Keyword(s):  
T Cell ◽  
T Lymphocyte ◽  
Antitumor Immunity ◽  
Cytotoxic T Lymphocyte ◽  
Cd4 T Cell ◽  
Lymphocyte Responses

scholarly journals Reduction of otherwise remarkably stable virus-specific cytotoxic T lymphocyte memory by heterologous viral infections.

1996 ◽  
Vol 183 (6) ◽  
pp. 2489-2499 ◽  
Author(s):  
L K Selin ◽  
K Vergilis ◽  
R M Welsh ◽  
S R Nahill
Keyword(s):  
Immune System ◽  
T Cell ◽  
T Lymphocyte ◽  
Viral Infections ◽  
Cytotoxic T Lymphocyte ◽  
Acute Infection ◽  
Cd8 T Cell ◽  
Infectious Agents ◽  
Acute Infections ◽  
Memory Pool

Experimental analyses of the acute cytotoxic T lymphocyte (CTL) response to viruses have focused on studying these infections in immunologically naive hosts. In the natural environment, however, viral CTL responses occur in hosts that are already immune to other infectious agents. To address which factors contribute to the maintenance and waning of immunological memory, the following study examined the frequencies of virus-specific CTL precursor cells (pCTL) not only using the usual experimental paradigm where mice undergo acute infections with a single virus, and in mice immune to a single virus, but also in immune mice after challenge with various heterologous viruses. As determined by limiting dilution assays, the pCTL frequency (p/f) per CD8+ T cell specific for lymphocytic choriomeningitis virus (LCMV), Pichinde virus (PV), or vaccinia virus (VV) increased during the acute infections, peaking at days 7-8 with frequencies as high as 1/27-1/74. Acute viral infections such as these elicit major expansions in the CD8+ T cell number, which has been reported to undergo apoptosis and decline after most of the viral antigen has been cleared. Although the decline in the total number of virus-specific pCTL after their peak in the acute infection was substantial, for all three viruses the virus-specific p/f per CD8+ T cell decreased only two- to fourfold and remained at these high levels with little fluctuation for well over a year. The ratios of the three immunodominant peptide-specific to total LCMV-specific clones remained unchanged between days 7 and 8 of acute infection and long-term memory, suggesting that the apoptotic events did not discriminate on the basis of T cell receptor specificity, but instead nonspecifically eliminated a large proportion of the activated T cells. However, when one to five heterologous viruses (LCMV, PV, VV, murine cytomegalovirus, and vesicular stomatitis virus) were sequentially introduced into this otherwise stable memory pool, the stability of the memory pool was disrupted. With each successive infection, after the immune system had returned to homeostasis, the memory p/f specific to viruses from earlier infections declined. Reductions in memory p/f were observed in all tested immunological compartments (spleen, peripheral blood, lymph nodes, and peritoneal cavity), and on average in the spleen revealed a 3 +/- 0.4-fold decrease in p/f after one additional viral infection and an 8.4 +/- 3-fold decrease after two additional viral infections. Thus, subsequent challenges with heterologous antigens, which themselves induce memory CTL, may contribute to the waning of CTL memory pool to earlier viruses as the immune system accommodates ever-increasing numbers of new memory cells within a limited lymphoid population. This demonstrates that virus infections do not occur in immunological isolation, and that CD8+ T cell responses are continually being modulated by other infectious agents.

scholarly journals Cytotoxic T Lymphocyte–associated Antigen 4 (CTLA-4) Can Regulate Dendritic Cell–induced Activation and Cytotoxicity of CD8+ T Cells Independently of CD4+T Cell Help

1999 ◽  
Vol 189 (7) ◽  
pp. 1157-1162 ◽  
Author(s):  
Kathy D. McCoy ◽  
Ian F. Hermans ◽  
J. Henry Fraser ◽  
Graham Le Gros ◽  
Franca Ronchese
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocyte ◽  
Cd8 T Cells ◽  
Cytotoxic T Lymphocyte ◽  
Cd4 T Cell ◽  
Cd4 T Cell Help ◽  
T Cell Help

The mechanisms that regulate the strength and duration of CD8+ cytotoxic T cell activity determine the effectiveness of an antitumor immune response. To better understand the antitumor effects of anti-cytotoxic T lymphocyte–associated antigen 4 (CTLA-4) antibody treatment, we analyzed the effect of CTLA-4 signaling on CD8+ T cells in vitro and in vivo. In vitro, cross-linking of CTLA-4 on purified CD8+ T cells caused decreased proliferative responses to anti-CD3 stimulation and rapid loss of activation marker expression. In vivo, blockade of CTLA-4 by neutralizing anti–CTLA-4 mAb greatly enhanced the accumulation, activation, and cytotoxic activity of CD8+ T cells induced by immunization with Ag on dendritic cells (DC). This enhanced response did not require the expression of MHC class II molecules on DC or the presence of CD4+ T cells. These results demonstrate that CTLA-4 blockade is able to directly enhance the proliferation and activation of specific CD8+ T cells, indicating its potential for tumor immunotherapy even in situations in which CD4+ T cell help is limited or absent.

Induction of novel CD8+ T-cell responses during chronic untreated HIV-1 infection by immunization with subdominant cytotoxic T-lymphocyte epitopes

AIDS ◽  
2009 ◽  
Vol 23 (11) ◽  
pp. 1329-1340 ◽  
Author(s):  
Henrik Kloverpris ◽  
Ingrid Karlsson ◽  
Jesper Bonde ◽  
Mette Thorn ◽  
Lasse Vinner ◽  
...  
Keyword(s):  
T Cell ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Cell Responses ◽  
Hiv 1

scholarly journals Human Immunodeficiency Virus-Specific CD8+ T-Cell Responses Do Not Predict Viral Growth and Clearance Rates during Structured Intermittent Antiretroviral Therapy

2002 ◽  
Vol 76 (20) ◽  
pp. 10169-10176 ◽  
Author(s):  
Annette Oxenius ◽  
Angela R. McLean ◽  
Marek Fischer ◽  
David A. Price ◽  
Sarah J. Dawson ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Cd8 T Cell ◽  
Viral Rebound ◽  
Clearance Rates ◽  
Cell Responses ◽  
Treatment Interruptions ◽  
Immunodeficiency Virus

ABSTRACT There is a continuing search for better ways to use existing drugs against human immunodeficiency virus (HIV). One idea is to use short therapy interruptions to “autovaccinate” HIV-infected patients. A group of 13 chronically HIV-infected patients enrolled in a trial of such so-called structured treatment interruptions (STIs) were intensively studied with respect to their viral load (VL) and HIV-specific CD8+ T-cell (cytotoxic T-lymphocyte [CTL]) responses. We found that 10 of the 13 patients had plateau VLs after STIs that were lower than their pretreatment VLs. While viral rebound rates became lower over STIs, there were no changes in clearance rates. Although numbers of CTLs did increase over the same time that viral rebounds decreased, there was no correlation between CTL count and either viral rebound rates or clearance rates. Finally, we asked whether absolute numbers of or changes in numbers of CTLs predict plateau VLs after STIs. No measure of CTLs was able to predict plateau VLs. Thus, there was no signature in these data of an important contribution to virological control from HIV-specific CD8+ T lymphocytes.

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