title: FOXP3 expressing CD127lo CD4+ T cells inversely correlate with CD38+ CD8+ T cell activation levels in primary HIV-1 infection.
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.
authors.affiliation: Division of Experimental Medicine, San Francisco General Hospital, University of California San Francisco, San Francisco, CA 94110, USA. lishomwa.ndhlovu@ucsf.edu
authors.forename: Lishomwa C
authors.initials: LC
authors.lastname: Ndhlovu
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Loo
authors.forename: Gerald
authors.initials: G
authors.lastname: Spotts
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Nixon
authors.forename: Frederick M
authors.initials: FM
authors.lastname: Hecht
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000032:analysis*; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002455:Cell Division; D018450:Disease Progression; D051858:Forkhead Transcription Factors / Q000032:analysis*; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1; D006801:Humans; D016130:Immunophenotyping; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D053699:Interleukin-7 Receptor alpha Subunit / Q000032:analysis*; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000032:analysis*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit; D053699:Interleukin-7 Receptor alpha Subunit; D008562:Membrane Glycoproteins; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1