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+IL-2+ and CD28+IL-2+ CD4 T Cell Responses Is Associated with Nonprogression in HIV-1 Infection1
Departments of
* Immunology and
HIV/Genitourinary Medicine, Guy’s, King’s, and St. Thomas’ School of Medicine and Dentistry, King’s College London, London, United Kingdom
HIV immunity is likely CD4 T cell dependent. HIV-specific CD4 T
cell proliferative responses are reported to correlate inversely with
virus load and directly with specific CD8 responses. However, the
phenotype and cytokine profile of specific CD4 T cells that correlate
with disease is unknown. We compared the number/function of Gag
p24-specific CD4 T cells in 17 HIV-infected long-term nonprogressors
(LTNPs) infected for a median of 14.6 years with those of 16 slow
progressors (SPs), also HIV infected for a median of 14 years but whose
CD4 count had declined to <500 cells/µl. Compared with SPs, LTNPs
had higher numbers of specific CD4s that were double positive for
IFN-
and IL-2 as well as CD28 and IL-2. However, CD4 T cells that
produced IL-2 alone (IL-2+IFN--) or IFN-
alone (IFN-+IL-2-) did not differ between
LTNPs and SPs. The decrease in p24-specific
CD28+IL-2+ cells with a concomitant increase of
p24-specific CD28-IL-2+ cells occurred before
those specific for a non-HIV Ag, CMV. p24-specific
CD28-IL-2+ cells were evident in LTNPs and
SPs, whereas the CMV-specific CD28-IL-2+
response was confined to SPs. The difference between LTNPs and SPs in
the Gag p24 IFN-+IL-2+ response was
maintained when responses to total Gag (p17 plus p24) were measured.
The percentage and absolute number of Gag-specific
IFN-+IL-2+ but not of
IFN-+IL-2- CD4s correlated inversely with
virus load. The Gag-specific IFN-+IL-2+ CD4
response also correlated positively with the percentage of Gag-specific
IFN-+ CD8 T cells in these subjects. Accumulation of
specific CD28-IL-2+ helpers and loss of
IFN-+IL-2+ CD4 T cells may compromise
specific CD8 responses and, in turn, immunity to
HIV.
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