Primary HIV-1 Infection Is Associated with Preferential Depletion of CD4+ T Lymphocytes from Effector Sites in the Gastrointestinal Tract

By S. Mehandru, M. Poles, K. Tenner‐Racz, A. Horowitz, A. Hurley, Christine M. Hogan, D. Boden, P. Rácz, M. Markowitz. Journal of Experimental Medicine, 2004

1,242 citations recorded by the source corpus.

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.

Subfields: Epidemiology, Infectious Diseases, Virology

View Paper: https://www.semanticscholar.org/paper/b1f805ee7a102e442471c230d25a31c3c7e8179d

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Infectious Diseases

1. Daniel C. Douek
2. Steven G. Deeks
3. C. K. Kwan
4. J. Ernst

In Virology

1. Daniel C. Douek
2. Steven G. Deeks
3. C. K. Kwan
4. J. Ernst

Citations in the corpus

• Dendritic-cell interactions with HIV: infection and viral dissemination (2006, background): “Also, because CD4 + T-cell populations in the gastrointestinal tract suffer the most marked depletion in both the acute and the chronic stage of HIV infectio”
• HIV and Tuberculosis: a Deadly Human Syndemic (2011, background): “The best-characterized and most important effect of HIV on immunity to TB and other infections is the depletion of CD4 T cells from secondary lymphoid tissues, peripheral blood, and mucosal sites such as the intestinal lamina propria (118, 180).”
• Relationship between T cell activation and CD4+ T cell count in HIV-seropositive individuals with undetectable plasma HIV RNA levels in the absence of therapy. (2008, background): “However, because T cell activation declines dramatically after initiation of antiretroviral therapy, long before significant restoration of CD4+ T cells in peripheral blood or tissues, T cell activation is unlikely to be solely a consequence of CD4+ T cell depletion in HIV infection [44, 45, 49].”
• Systemic effects of inflammation on health during chronic HIV infection. (2013, background): “With acute disease progression, microbial product translocation and its inflammatory effects becomes systemic (Brenchley et al., 2006; Burdo et al., 2011a; Hunt et al., 2012; Mehandru et al., 2004).”