Cycling of gut mucosal CD4+T cells decreases after prolonged anti-retroviral therapy and is associated with plasma LPS levels

被引：71

作者：

Ciccone, E. J. ^{[1
]}

Read, S. W. ^{[2
]}

Mannon, P. J. ^{[3
]}

Yao, M. D. ^{[4
]}

Hodge, J. N. ^{[1
]}

Dewar, R. ^{[5
]}

Chairez, C. L. ^{[1
]}

Proschan, M. A. ^{[6
]}

Kovacs, J. A. ^{[7
]}

Sereti, I. ^{[1
]}

机构：

[1] NIAID, Immunoregulat Lab, Bethesda, MD 20892 USA

[2] NIAID, Div Aids, Bethesda, MD 20892 USA

[3] Univ Alabama, Div Gastroenterol & Hepatol, Birmingham, AL USA

[4] NIAID, Host Def Lab, Bethesda, MD 20892 USA

[5] SAIC Frederick Inc, Frederick, MD USA

[6] NIAID, Biostat Res Branch, Bethesda, MD 20892 USA

[7] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA

来源：

MUCOSAL IMMUNOLOGY | 2010年 / 3卷 / 02期

基金：

美国国家卫生研究院;

关键词：

IMMUNODEFICIENCY-VIRUS TYPE-1; HIV-INFECTED PATIENTS; CD4(+) T-CELLS; MICROBIAL TRANSLOCATION; GASTROINTESTINAL-TRACT; LYMPHOID-TISSUE; IMMUNE RECONSTITUTION; PERIPHERAL-BLOOD; SIV INFECTION; LYMPHOCYTES;

D O I：

10.1038/mi.2009.129

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The gut mucosa is an important site of HIV immunopathogenesis with severe depletion of CD4+ T cells occurring during acute infection. The effect of prolonged anti-retroviral therapy (ART) on cycling and restoration of T lymphocytes in the gut remains unclear. Colon and terminal ileal biopsies and peripheral blood samples were collected from viremic, untreated, HIV-infected participants, patients treated with prolonged ART (>5 years), and uninfected controls and analyzed by flow cytometry. In the gut, the proportion of cycling T cells decreased and the number of CD4+ T cells normalized in treated patients in parallel with beta 7 expression on CD4+ T cells in blood. Cycling of gut T cells in viremic patients was associated with increased plasma LPS levels, but not colonic HIV-RNA. These data suggest that gut T-cell activation and microbial translocation may be interconnected whereas prolonged ART may decrease activation and restore gut CD4+ T cells.

引用

页码：172 / 181

页数：10

共 38 条

[1] Incomplete CD4 T cell recovery in HIV-1 infection after 12 months of highly active antiretroviral therapy is associated with ongoing increased CD4 T cell activation and turnover [J].

Anthony, KB ;

Yoder, C ;

Metcalf, JA ;

DerSimonian, R ;

Orenstein, JM ;

Stevens, RA ;

Falloon, J ;

Polis, MA ;

Lane, HC ;

Sereti, I .

JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES, 2003, 33 (02) :125-133

[2] Enhanced levels of functional HIV-1 co-receptors on human mucosal T cells demonstrated using intestinal biopsy tissue [J].

Anton, PA ;

Elliott, J ;

Poles, MA ;

McGowan, IM ;

Matud, J ;

Hultin, LE ;

Grovit-Ferbas, K ;

Mackay, CR ;

Chen, ISY ;

Giorgi, JV .

AIDS, 2000, 14 (12) :1761-1765

[3] HIV-1 envelope protein binds to and signals through integrin α4β7, the gut mucosal homing receptor for peripheral T cells [J].

Arthos, James ;

Cicala, Claudia ;

Martinelli, Elena ;

Macleod, Katilyn ;

Van Ryk, Donald ;

Wei, Danlan ;

Xiao, Zhen ;

Veenstra, Timothy D. ;

Conrad, Thomas P. ;

Lempicki, Richard A. ;

McLaughlin, Sherry ;

Pascuccio, Massimiliano ;

Gopaul, Ravindra ;

McNally, Jonathan ;

Cruz, Catherine C. ;

Censoplano, Nina ;

Chung, Eva ;

Reitano, Kristin N. ;

Kottilil, Shyam ;

Goode, Diana J. ;

Fauci, Anthony S. .

NATURE IMMUNOLOGY, 2008, 9 (03) :301-309

[4] Microbial translocation is a cause of systemic immune activation in chronic HIV infection [J].

Brenchley, Jason M. ;

Price, David A. ;

Schacker, Timothy W. ;

Asher, Tedi E. ;

Silvestri, Guido ;

Rao, Srinivas ;

Kazzaz, Zachary ;

Bornstein, Ethan ;

Lambotte, Olivier ;

Altmann, Daniel ;

Blazar, Bruce R. ;

Rodriguez, Benigno ;

Teixeira-Johnson, Leia ;

Landay, Alan ;

Martin, Jeffrey N. ;

Hecht, Frederick M. ;

Picker, Louis J. ;

Lederman, Michael M. ;

Deeks, Steven G. ;

Douek, Daniel C. .

NATURE MEDICINE, 2006, 12 (12) :1365-1371

[5] CD4+ T cell depletion during all stages of HIV disease occurs predominantly in the gastrointestinal tract [J].

Brenchley, JM ;

Schacker, TW ;

Ruff, LE ;

Price, DA ;

Taylor, JH ;

Beilman, GJ ;

Nguyen, PL ;

Khoruts, A ;

Larson, M ;

Haase, AT ;

Douek, DC .

JOURNAL OF EXPERIMENTAL MEDICINE, 2004, 200 (06) :749-759

[6] Persistence of HIV in gut-associated lymphoid tissue despite long-term antiretroviral therapy [J].

Chun, Tae-Wook ;

Nickle, David C. ;

Justement, Jesse S. ;

Meyers, Jennifer H. ;

Roby, Gregg ;

Hallahan, Claire W. ;

Kottilil, Shyam ;

Moir, Susan ;

Mican, Joann M. ;

Mullins, James I. ;

Ward, Douglas J. ;

Kovacs, Joseph A. ;

Mannon, Peter J. ;

Fauci, Anthony S. .

JOURNAL OF INFECTIOUS DISEASES, 2008, 197 (05) :714-720

[7] Selective depletion of rectal lamina propria rather than lymphoid aggregate CD4 lymphocytes HIV infection [J].

Clayton, F ;

Snow, G ;

Reka, S ;

Kotler, DP .

CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 1997, 107 (02) :288-292

[8]

CONNICK E, 2007, C RETR OPP INF 26 FE

[9] 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].

George, MD ;

Reay, E ;

Sankaran, S ;

Dandekar, S .

JOURNAL OF VIROLOGY, 2005, 79 (05) :2709-2719

[10] 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].

Guadalupe, M ;

Reay, E ;

Sankaran, S ;

Prindiville, T ;

Flamm, J ;

McNeil, A ;

Dandekar, S .

JOURNAL OF VIROLOGY, 2003, 77 (21) :11708-11717

← 1 2 3 4 →