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Published online before print November 2, 2007

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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0507281

Received for publication May 4, 2007.
Revised October 9, 2007.
Accepted for publication October 9, 2007.

Article

FOXP3 expressing CD127lo CD4+ T cells inversely correlates with CD38+ CD8+ T cell activation levels in primary HIV-1 infection

Lishomwa C. Ndhlovu ^*@, Christopher P. Loo ^*, Gerald Spotts , Douglas F. Nixon ^*, and Frederick M. Hecht

*Division of Experimental Medicine and Positive Health Program, Department of Medicine, San Francisco General Hospital, University of California San Francisco, San Francisco, California, USA

^@ To whom correspondence should be addressed. E-mail: lishomwa.ndhlovu{at}ucsf.edu.

	Abstract

During the course of HIV-1 infection, the status of immune activation has been determined to be a powerful indicator of disease progression. The immune system has adopted self-regulatory mechanisms to counterbalance undesirable immune responses. CD25+CD4+ T regulatory (Treg) cells that express the transcription regulator, forkhead box P3 (FOXP3), play an important role in this immunosuppression. Using a combination of Treg cell discriminatory markers (FOXP3, CD25, CD127), we predicted that an expansion of Treg cell subsets would negatively correlate with immune activation during the early stages of HIV-1 infection. We report that FOXP3+CD127lo expressing CD4+ T cells increases in primary HIV-1 infection over time. Furthermore, the FOXP3+CD127lo CD4+ T cells may, in fact, reduce the levels of T cell activation following primary infection. It is interesting that the positive correlation between FOXP3+CD127lo CD4+ and CD25+CD127lo CD4+ T cells noted in HIV-uninfected persons is not only lost but may also be reversed in early, chronic HIV-1 infection. Unlike FOXP3+CD127lo CD4+, the level of FOXP3+CD25+CD127lo CD4+ T cells did not correlate with T cell activation, suggesting that these cells were not effective in reducing T cell activation. These observations suggest that different Treg populations may have different effects on reducing immune activation in HIV-1 infection and that the FOXP3+CD127lo CD4+ T cell population may be particularly important in limiting immune activation.

Key Words: regulation • immunosuppression • viral • AIDS

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