CD25(+)CD4(+) regulatory T cells from the peripheral blood of asymptomatic HIV-infected individuals regulate CD4(+) and CD8(+) HIV-specific T cell immune responses in vitro and are associated with favorable clinical markers of disease status.
Human immunodeficiency virus (HIV) disease is associated with loss of CD4(+) T cells, chronic immune activation, and progressive immune dysfunction. HIV-specific responses, particularly those of CD4(+) T cells, become impaired early after infection, before the loss of responses directed against other antigens; the basis for this diminution has not been elucidated fully. The potential role of CD25(+)CD4(+) regulatory T cells (T reg cells), previously shown to inhibit immune responses directed against numerous pathogens, as suppressors of HIV-specific T cell responses was investigated. In the majority of healthy HIV-infected individuals, CD25(+)CD4(+) T cells significantly suppressed cellular proliferation and cytokine production by CD4(+) and CD8(+) T cells in response to HIV antigens/peptides in vitro; these effects were cell contact dependent and IL-10 and TGF-beta independent. Individuals with strong HIV-specific CD25(+) T reg cell function in vitro had significantly lower levels of plasma viremia and higher CD4(+): CD8(+) T cell ratios than did those individuals in whom this activity could not be detected. These in vitro data suggest that CD25(+)CD4(+) T reg cells may contribute to the diminution of HIV-specific T cell immune responses in vivo in the early stages of HIV disease.
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, 10 Center Dr., Bethesda, MD 20892, USA. AKinter@niaid.nih.gov
Audrey L
AL
Kinter
Margaret
M
Hennessey
Alicia
A
Bell
Sarah
S
Kern
Yin
Y
Lin
Marybeth
M
Daucher
Maria
M
Planta
Mary
M
McGlaughlin
Robert
R
Jackson
Steven F
SF
Ziegler
Anthony S
AS
Fauci
D015704:CD4 Antigens / Q000032:analysis / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D006678:HIV / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D016753:Interleukin-10 / Q000502:physiology; D008213:Lymphocyte Activation; D015375:Receptors, Interleukin-2 / Q000032:analysis*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000502:physiology
D015704:CD4 Antigens; D016207:Cytokines; D015375:Receptors, Interleukin-2; D016212:Transforming Growth Factor beta; D016753:Interleukin-10