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Originally published online as doi:10.1189/jlb.0708438 on September 19, 2008

Published online before print September 19, 2008
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(Journal of Leukocyte Biology. 2008;84:1447-1453.)
© 2008 by Society for Leukocyte Biology

Immune activation and IL-12 production during acute/early HIV infection in the absence and presence of highly active, antiretroviral therapy

Adriana A. Byrnes*,{dagger}, David M. Harris*,{dagger}, Sowsan F. Atabani{ddagger}, Beulah P. Sabundayo*,{dagger}, Susan J. Langan{dagger}, Joseph B. Margolick{dagger} and Christopher L. Karp*,{dagger},{ddagger},1

* Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA;
{dagger} Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA; and
{ddagger} Division of Molecular Immunology, Cincinnati Children’s Hospital Research Foundation, and the University of Cincinnati College of Medicine, Cincinnati, Ohio, USA

1 Correspondence: Division of Molecular Immunology, Cincinnati Children’s Hospital Research Foundation, 3333 Burnet Avenue, Cincinnati, OH 45229, USA. E-mail: chris.karp{at}chmcc.org

ABSTRACT

Suppressed IL-12 production and maladaptive immune activation, both of which are ameliorated by successful highly active antiretroviral therapy (HAART), are thought to play important roles in the immunopathogenesis of chronic HIV infection. Despite the important effects of the immunological and virological events of early HIV infection on subsequent disease progression, IL-12 production and immune activation in early infection remain under-defined. To quantify IL-12 production and immune activation during acute/early HIV infection, in the presence and absence of HAART, we performed a prospective, longitudinal study of participants in the Baltimore site of the Acute Infection and Early Disease Research Program, with cross-sectional comparison to healthy control subjects. PBMC cytokine productive capacity and plasma immune activation markers [soluble CD8 (sCD8), sCD4, granzyme B, neopterin, β2-microglobulin, sIL-2R, sTNFRI, sTNFRII, and IL-12p70] were quantified by ELISA. Notably, PBMC from patients with acute/early HIV infection exhibited in vivo IL-12p70 production along with increased, maximal in vitro IL-12 production. Further, despite evidence from plasma markers of generalized immune activation, no elevation in plasma levels of sCD4 was observed, suggesting relative blunting of in vivo CD4+ T cell activation from the beginning of HIV infection. Finally, despite successful virological responses to HAART, heightened in vivo CD8+ T cell activation, IL-12 production, and IFN activity were sustained for at least 6 months during primary HIV infection. These data underscore the need for comparative mechanistic analysis of the immunobiology of early and chronic HIV infection.

Key Words: regulation • cytokine • interferon