4th International AIDS Society Conference on HIV Pathogenesis and Treatment Sydney, Australia - July 22 - 25, 2007

REGULATORY T CELLS IN INFANT MACAQUES SUPPRESS ANTI-SIV RESPONSES AMONG CD4+ T CELLS

IAS Conf HIV Pathog Treat 2007 Jul 22-25;4th: Abstract No. MOAA102

Hartigan-OConnor D.¹, Abel K.², McCune J.M.^1
1University of California, Division of Experimental Medicine, San Francisco, United States, ²University of California, California National Primate Research Center, Davis, United States

OBJECTIVES: The impact of regulatory T cells (T-regs) on the course of HIV and SIV disease remains unclear. We found that infant macaque blood and tissue samples contain more regulatory T cells than adult samples and that these infant T-regs exhibit greater in vitro suppressive activity. We tested the impact of regulatory T cells on antiviral T cell responses by using infant and adult macaques as models of infected patients with high and low regulatory T cell numbers, respectively.

METHODS: We followed immune responses and the course of SIV disease in infant macaques, containing an average of 10% T-regs among CD4+ cells, and adult macaques, containing on average only 4% T-regs. SIV-specific T cell responses were tested in the presence and absence of CD25+ T-regs. By comparing anti-SIV immune responses among infants, harboring many T-regs, and adults, harboring few T-regs, we sought to understand the importance of regulatory T cell numbers for anti-SIV responses.

RESULTS: Infant macaques mounted only transient CD8+ T cell responses to SIV during the first two weeks of infection, while adult macaques maintained CD8+ T cell responses throughout infection. Depletion assays showed, however, that infant SIV-specific CD8+ T cells were not directly inhibited by T-regs. Infant SIV-specific CD4+ T cells expressing IL-2 and IFN-γ, however, were directly inhibited by T-regs throughout infection and were detectable only after depletion of CD25+ cells. SIV-specific CD4+ T cells were consistently detected in adults, whether in the presence or absence of T-regs.

CONCLUSIONS: The presence of larger numbers of regulatory T cells among infant macaques is associated with active suppression of CD4+ T cells throughout infection and early failure of SIV-specific CD8+ T cell responses. Our findings implicate T-regs as potentially important direct antagonists of multifunctional CD4+ T cell responses and indirect antagonists of antiviral CD8+ T cell responses.

Download PDF of this abstract.

2007-07-22
MOAA102
Immune Activation in HIV Pathogenesis

Copyright © 2007 - International AIDS Society (IAS). All information and content relating to the abstracts from the 3rd International AIDS Society Conference on HIV Pathogenesis and Treatment, such as text, graphics, logos, button icons, images, audio clips, and software is protected by copyright. Permission is hereby granted for the non-commercial use or reproduction of the information on this web site, provided that the use of such information is accompanied by an acknowledgement that IAS is the source of the information and the name of the author of the article.

AEGiS is made possible through unrestricted funding from Boehringer Ingelheim, Bridgestone/Firestone Charitable Trust, Bristol-Myers Squibb Company, Elton John AIDS Foundation, the National Library of Medicine, and donations from users like you. Always watch for outdated information. This article first appeared in 2007. This material is designed to support, not replace, the relationship that exists between you and your doctor.

AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.

Copyright ©1980, 2007. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content. Permission is hereby granted for the non-commercial use or reproduction of the information herein, provided that the use of such information is accompanied by an acknowledgement that IAS is the source of the information and the name of the author of the article.