Naive T-cell depletion related to infection by X4 human immunodeficiency virus type 1 in poor immunological responders to highly active antiretroviral therapy

被引:55
作者
Delobel, Pierre
Nugeyre, Marie-Therese
Cazabat, Michelle
Sandres-Saune, Karine
Pasquier, Christophe
Cuzin, Lise
Marchou, Bruno
Massip, Patrice
Cheynier, Remi
Barre-Sinoussi, Francoise
Izopet, Jacques
Israel, Nicole
机构
[1] CHU Purpan, Virol Lab, EA2046, IFR30, F-31059 Toulouse 9, France
[2] Inst Pasteur, Unite Regulat Infect Retrovirales, Paris, France
[3] CHU Toulouse, Serv Malad Infect & Trop, Toulouse, France
[4] Inst Pasteur, Unite Virus Lents, Paris, France
关键词
D O I
10.1128/JVI.00965-06
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
The reasons for poor CD4(+) T-cell recovery in some human immunodeficiency virus (HIV)-infected subjects despite effective highly active antiretroviral therapy (HAART) remain unclear. We recently reported that CXCR4-using (X4) HIV-1 could be gradually selected in cellular reservoirs during sustained HAART. Because of the differential expression of HIV-1 coreceptors CCR5 and CXCR4 on distinct T-cell subsets, the residual replication of R5 and X4 viruses could have different impacts on T-cell homeostasis during immune reconstitution on HAART. We examined this hypothesis and the mechanisms of CD4(+) T-cell restoration by comparing the virological and immunological features of 15 poor and 15 good immunological responders to HAART. We found a high frequency of X4 viruses in the poor immunological responders. But the levels of intrathymic proliferation of the two groups were similar regardless of whether they were infected by R5 or X4 virus. The frequency of recent thymic emigrants in the poor immunological responders was also similar to that found in the good immunological responders, despite their reduced numbers of naive CD4(+) T cells. Our data, rather, suggest that the naive T-cell compartment is drained by a high rate of mature naive cell loss in the periphery due to bystander apoptosis or activation-induced differentiation. X4 viruses could play a role in the depletion of naive T cells in poor immunological responders to HAART by triggering persistent T-cell activation and bystander apoptosis via gpl20-CXCR4 interactions.
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页码:10229 / 10236
页数:8
相关论文
共 45 条
[31]   Dynamics of T cells and TCR excision circles differ after treatment of acute and chronic HIV Infection [J].
Lewin, SR ;
Ribeiro, RM ;
Kaufmann, GR ;
Smith, D ;
Zaunders, J ;
Law, M ;
Solomon, A ;
Cameron, PU ;
Cooper, D ;
Perelson, AS .
JOURNAL OF IMMUNOLOGY, 2002, 169 (08) :4657-4666
[32]   Peak SIV replication in resting memory CD4+ T cells depletes gut lamina propria CD4+ T cells [J].
Li, QS ;
Duan, LJ ;
Estes, JD ;
Ma, ZM ;
Rourke, T ;
Wang, YC ;
Reilly, C ;
Carlis, J ;
Miller, CJ ;
Haase, AT .
NATURE, 2005, 434 (7037) :1148-1152
[33]   Massive infection and loss of memory CD4+ T cells in multiple tissues during acute SIV infection [J].
Mattapallil, JJ ;
Douek, DC ;
Hill, B ;
Nishimura, Y ;
Martin, M ;
Roederer, M .
NATURE, 2005, 434 (7037) :1093-1097
[34]   High prevalence of thymic tissue in adults with human immunodeficiency virus-1 infection [J].
McCune, JM ;
Loftus, R ;
Schmidt, DK ;
Carroll, P ;
Webster, D ;
Swor-Yim, LB ;
Francis, IR ;
Gross, BH ;
Grant, RM .
JOURNAL OF CLINICAL INVESTIGATION, 1998, 101 (11) :2301-2308
[35]   Resting naive CD4+ T cells are massively infected and eliminated by X4-tropic simian-human immunodeficiency viruses in macaques [J].
Nishimura, Y ;
Brown, CR ;
Mattapallil, JJ ;
Igarashi, T ;
Buckler-White, A ;
Lafont, BAP ;
Hirsch, VM ;
Roederer, M ;
Martin, MA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (22) :8000-8005
[36]   De novo T-cell generation in patients at different ages and stages of HIV-1 disease [J].
Nobile, M ;
Correa, R ;
Borghans, JAM ;
D'Agostino, C ;
Schneider, P ;
de Boer, RJ ;
Pantaleo, G .
BLOOD, 2004, 104 (02) :470-477
[37]   Persistence of HIV-1 structural proteins and glycoproteins in lymph nodes of patients under highly active antiretroviral therapy [J].
Popovic, M ;
Tenner-Racz, K ;
Pelser, C ;
Stellbrink, HJ ;
van Lunzen, J ;
Lewis, G ;
Kalyanaraman, VS ;
Gallo, RC ;
Racz, P .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (41) :14807-14812
[38]   The decay of the latent reservoir of replication-competent HIV-1 is inversely correlated with the extent of residual viral replication during prolonged anti-retroviral therapy [J].
Ramratnam, B ;
Mittler, JE ;
Zhang, LQ ;
Boden, D ;
Hurley, A ;
Fang, F ;
Macken, CA ;
Perelson, AS ;
Markowitz, M ;
Ho, DD .
NATURE MEDICINE, 2000, 6 (01) :82-85
[39]   Selection of human immunodeficiency virus type 1 R5 variants with augmented replicative capacity and reduced sensitivity to entry inhibitors during severe immunodeficiency [J].
Repits, J ;
Öberg, M ;
Esbjörnsson, J ;
Medstrand, P ;
Karlsson, A ;
Albert, J ;
Fenyö, EM ;
Jansson, M .
JOURNAL OF GENERAL VIROLOGY, 2005, 86 :2859-2869
[40]   Induction of simian AIDS in infant rhesus Macaques infected with CCR5- or CXCR4-utilizing Simian-human immunodeficiency viruses is associated with distinct lesions of the thymus [J].
Reyes, RA ;
Canfield, DR ;
Esser, U ;
Adamson, LA ;
Brown, CR ;
Cheng-Mayer, C ;
Gardner, MB ;
Harouse, JM ;
Luciw, PA .
JOURNAL OF VIROLOGY, 2004, 78 (04) :2121-2130