Primary HIV-1 infection is associated with preferential depletion of CD4+ T lymphocytes from effector sites in the gastrointestinal tract.
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.
Mehandru
Saurabh
S
Aaron Diamond AIDS Research Center, The Rockefeller University, 455 First Ave., 7th Fl., New York, NY 10016, USA.
Poles
Michael A
MA
Tenner-Racz
Klara
K
Horowitz
Amir
A
Hurley
Arlene
A
Hogan
Christine
C
Boden
Daniel
D
Racz
Paul
P
Markowitz
Martin
M
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000276:immunology*; D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004064:Digestive System / Q000276:immunology* / Q000821:virology; D015497:HIV-1; D006801:Humans; D007413:Intestinal Mucosa / Q000276:immunology; D019713:Receptors, CCR5 / Q000032:analysis
D019713:Receptors, CCR5