Maintenance of HIV-specific CD4+ T cell help distinguishes HIV-2 from HIV-1 infection.
Unlike HIV-1-infected people, most HIV-2-infected subjects maintain a healthy CD4+ T cell count and a strong HIV-specific CD4+ T cell response. To define the cellular immunological correlates of good prognosis in HIV-2 infection, we conducted a cross-sectional study of HIV Gag-specific T cell function in HIV-1- and HIV-2-infected Gambians. Using cytokine flow cytometry and lymphoproliferation assays, we show that HIV-specific CD4+ T cells from HIV-2-infected individuals maintained proliferative capacity, were not terminally differentiated (CD57-), and more frequently produced IFN-gamma or IL-2 than CD4+ T cells from HIV-1-infected donors. Polyfunctional (IFN-gamma+/IL-2+) HIV-specific CD4+ T cells were found exclusively in HIV-2+ donors. The disparity in CD4+ T cell responses between asymptomatic HIV-1- and HIV-2-infected subjects was not associated with differences in the proliferative capacity of HIV-specific CD8+ T cells. This study demonstrates that HIV-2-infected donors have a well-preserved and functionally heterogeneous HIV-specific memory CD4+ T cell response that is associated with delayed disease progression in the majority of infected people.
Duvall
Melody G
MG
Medical Research Council (MRC) Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
Jaye
Assan
A
Dong
Tao
T
Brenchley
Jason M
JM
Alabi
Abraham S
AS
Jeffries
David J
DJ
van der Sande
Marianne
M
Togun
Toyin O
TO
McConkey
Samuel J
SJ
Douek
Daniel C
DC
McMichael
Andrew J
AJ
Whittle
Hilton C
HC
Koup
Richard A
RA
Rowland-Jones
Sarah L
SL
D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D018959:CD57 Antigens / Q000096:biosynthesis / Q000097:blood; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000821:virology; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D003430:Cross-Sectional Studies; D018450:Disease Progression; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D015683:Gene Products, gag / Q000097:blood / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D020276:HIV Long-Term Survivors; D015497:HIV-1 / Q000276:immunology*; D015498:HIV-2 / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000097:blood; D007376:Interleukin-2 / Q000096:biosynthesis / Q000097:blood; D007424:Intracellular Fluid / Q000276:immunology / Q000378:metabolism / Q000821:virology
D018959:CD57 Antigens; D018984:Epitopes, T-Lymphocyte; D015683:Gene Products, gag; D007376:Interleukin-2; D007371:Interferon-gamma