Decimated or missing in action: CD4+ T cells as targets and effectors in the pathogenesis of primary HIV infection

被引:17
作者
Kelleher A.D. [1 ]
Zaunders J.J. [1 ]
机构
[1] Immunovirology and Pathogenesis Program, National Centre in HIV Epidemiology and Clinical Research, University of North South Wales, Darlinghurst, NSW 2010
关键词
Memory Cell; Inductive Site; Profound Depletion; Preferential Depletion; Term Nonprogressors;
D O I
10.1007/s11904-006-0002-5
中图分类号
学科分类号
摘要
HIV infection provides a unique challenge to the immune system. CD4+ T cells are targets of infection, whereas effective anti-HIV CD4+ T-cell responses are essential for sustained viral control. There is increasing evidence of preferential depletion of certain subsets of CD4+ T cells. Studies of tissues have demonstrated preferential depletion of CD4+ T cells from gastrointestinal lymphoid tissue (GALT). Simian immunodeficiency virus infection of macaques results in extensive depletion of CD4+ memory T cells from GALT within weeks of infection. Other macaque studies suggest this rapid, profound depletion is generalized across all lymphoid tissue. Although these models provide insight into possible pathogenic processes, these results cannot be directly extrapolated to HIV infection in humans. Although there is depletion of CD4+ T cell memory cells early in HIV infection, the mechanism of this depletion appears to be related to increased cell turnover, chronicity of antigen exposure, and ineffective production of central memory CD4+ T cells rather than only direct cell depletion. Copyright © 2006 by Current Science Inc.
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页码:5 / 12
页数:7
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共 74 条
[31]  
Mehandru S., Poles M.A., Tenner-Racz K., Et al., Primary HIV-1 infection is associated with preferential depletion of CD4+ T lymphocytes from effector sites in the gastrointestinal tract, J Exp Med, 200, pp. 761-770, (2004)
[32]  
Guadalupe M., Reay E., Sankaran S., Et al., Severe CD4+ T-cell depletion in gut lymphoid tissue during primary human immunodeficiency virus type 1 infection and substantial delay in restoration following highly active antiretroviral therapy, J Virol, 77, pp. 11708-11717, (2003)
[33]  
Brenchley J.M., Schacker T.W., Ruff L.E., Et al., CD4+ T cell depletion during all stages of HIV disease occurs predominantly in the Gastrointestinal tract, J Exp Med, 200, pp. 749-759, (2004)
[34]  
Zhang Z.-Q., Wietgrefe S.W., Li Q., Et al., Roles of substrate availability and infection of resting and activated CD4+ T cells in transmission and acute simian immunodeficiency virus infection, Proc Natl Acad Sci U S A, 101, pp. 5640-5645, (2004)
[35]  
Westendorp M.O., Frank R., Oschenbauer C., Et al., Sensitization of T cells to CD95-mediated apoptosis by HIV-1 Tat and gp120, Nature, 375, pp. 497-500, (1995)
[36]  
Couedel-Courteille A., Pretet J.L., Barget N., Et al., Delayed viral replication and CD4(+) T cell depletion in the rectosigmoid mucosa of macaques during primary rectal SIV infection, Virology, 316, pp. 290-301, (2003)
[37]  
Ling B., Veazey R.S., Luckay A., Et al., SIV(mac) pathogenesis in rhesus macaques of Chinese and Indian origin compared with primary HIV infections in humans, AIDS, 16, pp. 1489-1496, (2002)
[38]  
George M.D., Reay E., Sankaran S., Dandekar S., Early antiretroviral therapy for simian immunodeficiency virus infection leads to mucosal CD4+ T-cell restoration and enhanced gene expression regulating mucosal repair and regeneration, J Virol, 79, pp. 2709-2719, (2005)
[39]  
Schenkel A.R., Uno H., Pauza D., Asymptomatic simian immunodeficiency virus infection decreases blood CD4+ T cells by accumulating recirculating lymphocytes in the lymphoid tissue, J Virol, 73, pp. 601-607, (1999)
[40]  
Sopper S., Niewetberg D., Halbach A., Et al., Impact of simian immunodeficiency virus (SIV) infection on lymphocyte numbers and T-cell turnover in different organs of rhesus monkeys, Blood, 101, pp. 1213-1219, (2003)