Open AccessMechanisms of Gastrointestinal CD4+T-Cell Depletion during Acuteand Early Human Immunodeficiency Virus Type 1 Infection
Author(s) -
Saurabh Mehandru,
Michael A. Poles,
Klara Tenner-Rácz,
Victoria Manuelli,
Patrick Jean-Pierre,
Peter Lopez,
Anita Shet,
Andrea Low,
Hiroshi Mohri,
Daniel Boden,
Paul Rácz,
Martin Markowitz
Publication year - 2007
Publication title -
journal of virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.617
H-Index - 292
eISSN - 1070-6321
pISSN - 0022-538X
DOI - 10.1128/jvi.01739-06
Subject(s) - biology , lamina propria , cytotoxic t cell , flow cytometry , in situ hybridization , immunohistochemistry , virology , microbiology and biotechnology , gastrointestinal tract , virus , simian immunodeficiency virus , immunology , in vitro , messenger rna , epithelium , gene , biochemistry , genetics
Duringacute and early human immunodeficiency virus type 1 (HIV-1) infection(AEI) more than 50% of CD4+ T cells arepreferentially depleted from the gastrointestinal (GI) lamina propria.To better understand the underlying mechanisms, we studied virologicaland immunological events within the peripheral blood (PB) and GI tractduring AEI. A total of 32 AEI subjects and 18 uninfected controlsunderwent colonic biopsy. HIV-1 viral DNA and RNA levels werequantified in CD4+ T cells derived from the GI tractand PB by using real-time PCR. The phenotype of infected cells wascharacterized by using combinations of immunohistochemistry and in situhybridization. Markers of immunological memory, activation, andproliferation were examined by flow cytometry and immunohistochemistry,and the host-derived cytotoxic cellular response was examined by usingimmunohistochemistry. GI CD4+ T cells harbored, onaverage, 13-fold higher HIV-1 viral DNA levels and 10-fold higher HIV-1RNA levels than PB CD4+ T cells during AEI. HIV-1RNA was detected in both “activated” and“nonactivated” mucosal CD4+ T cells.A significantly higher number of activated and proliferating T cellswere detected in the GI tract compared to the PB, and a robustcytotoxic response (HIV-1 specificity not determined) was detected inthe GI tract as early as 18 days postinfection. MucosalCD4+ T-cell depletion is multifactorial. Directviral infection likely accounts for the earliest loss ofCD4+ T cells. Subsequently, ongoing infection ofsusceptible CD4+ T cells, along withactivation-induced cellular death and host cytotoxic cellular response,are responsible for the persistence of thelesion.