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Blood, 1 August 2004, Vol. 104, No. 3, pp. 775-780.
Prepublished online as a Blood First Edition Paper on April 13, 2004; DOI 10.1182/blood-2003-12-4355.
 Previous Article | Next Article 
Submitted December 22, 2003
Accepted March 26, 2004
IL-2 Induced CD4+ T Cell Expansion in HIV-Infected Patients Is Associated with Long-Term Decreases in T Cell Proliferation
Irini Sereti*, Kara B Anthony, Hector Martinez-Wilson, Richard Lempicki, Joseph Adelsberger, Julia A Metcalf, Claire W Hallahan, Dean Follmann, Richard T Davey, Joseph A Kovacs, and H C Lane
National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
Science Applications International Corp., Science National Cancer Institute, Frederick, MD, USA
Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD, USA
* Corresponding author; email: isereti{at}niaid.nih.gov.
IL-2 administration leads to selective and sustained CD4+ T cell expansions in HIV infected patients. It has been hypothesized that persistent CD4+ T cell proliferation is the primary mechanism maintaining these expansions. T cell proliferation was studied by ex vivo BrdU incorporation and intracellular Ki67 staining in HIV infected patients treated with antiretroviral therapy (ART) with or without IL-2. In contrast to the tested hypothesis, IL-2 treated HIV-infected patients had lower CD4+ T cell proliferation compared to patients treated with ART alone. Independently of viral load changes, administration of IL-2 led to a decrease in basal CD4+ T cell proliferation. Total numbers of CD4+ T cells with naive and recall, but not effector, memory phenotype were increased. The degree of CD4+ T cell expansion correlated with the decreases in prolifertion and a strong association was seen between these decreases and the expansion of the CD4+/CD25+ subset. Intermittent IL-2 in HIV infected patients leads to expansions of CD4+/CD25+ T cells with naive and recall memory phenotypes that strongly correlate with decreases in proliferation. These data suggest that decreased T cell proliferation is central in the CD4+ T cell expansions induced by IL-2.
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