The Journal of Experimental Medicine
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Published online 13 September 2004 doi:10.1084/jem.20041196
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 200, Number 6, 761-770
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Primary HIV-1 Infection Is Associated with Preferential Depletion of CD4+ T Lymphocytes from Effector Sites in the Gastrointestinal Tract

Saurabh Mehandru1, Michael A. Poles1,2, Klara Tenner-Racz3, Amir Horowitz1,2, Arlene Hurley1, Christine Hogan1, Daniel Boden1, Paul Racz3, and Martin Markowitz1

1 Aaron Diamond AIDS Research Center and The Rockefeller University, New York, NY 10016
2 New York University School of Medicine, New York, NY 10016
3 Bernhard-Nocht Institut Fur Tropenmedizin, 20359 Hamburg, Germany

Address correspondence to Martin Markowitz, Aaron Diamond AIDS Research Center, The Rockefeller University, 455 First Ave., 7th Fl., New York, NY 10016. Phone: (212) 448-5020; Fax: (212) 725-1126; email: mmarkowitz{at}adarc.org

Given its population of CCR5-expressing, immunologically activated CD4+ T cells, the gastrointestinal (GI) mucosa is uniquely susceptible to human immunodeficiency virus (HIV)-1 infection. We undertook this study to assess whether a preferential depletion of mucosal CD4+ T cells would be observed in HIV-1–infected subjects during the primary infection period, to examine the anatomic subcompartment from which these cells are depleted, and to examine whether suppressive highly active antiretroviral therapy could result in complete immune reconstitution in the mucosal compartment. Our results demonstrate that a significant and preferential depletion of mucosal CD4+ T cells compared with peripheral blood CD4+ T cells is seen during primary HIV-1 infection. CD4+ T cell loss predominated in the effector subcompartment of the GI mucosa, in distinction to the inductive compartment, where HIV-1 RNA was present. Cross-sectional analysis of a cohort of primary HIV-1 infection subjects showed that although chronic suppression of HIV-1 permits near-complete immune recovery of the peripheral blood CD4+ T cell population, a significantly greater CD4+ T cell loss remains in the GI mucosa, despite up to 5 yr of fully suppressive therapy. Given the importance of the mucosal compartment in HIV-1 pathogenesis, further study to elucidate the significance of the changes observed here is critical.

Key Words: primary HIV-1 • GALT • CD4+ T cells

S. Mehandru and M.A. Poles contributed equally to this work.

A portion of this data was presented in abstract forms at Digestive Disease Week, May 2004 (New Orleans, LA) and the second international workshop for acute and early HIV-1 infection, May 2004 (Bethesda, MD). No similar paper has been or will be submitted elsewhere.

Abbreviations used in this paper: GALT, gut-associated lymphoid tissue; GI, gastrointestinal; HAART, highly active antiretroviral therapy; MMC, mucosal mononuclear cell; SIV, simian immunodeficiency.


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