Nef-specific CD45RA+CD8+T cells secreting MIP-1 beta but not IFN-gamma are associated with nonprogressive HIV-1 infection

Background: Long-term survival of HIV-1 infected individuals is
usually achieved by continuous administration of combination
antiretroviral therapy (ART). An exception to this scenario is
represented by HIV-1 infected nonprogressors (NP) which maintain
relatively high circulating CD4+ T cells without clinical symptoms
for several years in the absence of ART. Several lines of evidence
indicate an important role of the T-cell response in the modulation
of HIV-1 infection during the acute and chronic phase of the
disease. Results: We analyzed the functional and the
differentiation phenotype of Nef- and Tat-specific CD8+ T cells in
a cohort of HIV-1 infected NP in comparison to progressors,
ART-treated seropositive individuals and individuals undergoing a
single cycle of ART interruption. We observed that a distinctive
feature of NP is the presence of Nef-specific CD45RA+ CD8+ T cells
secreting MIP-1beta but not IFN-gamma. This population was present
in 7 out of 11 NP. CD45RA+ IFN-gamma(neg) MIP-1beta+ CD8+ T cells
were not detected in HIV-1 infected individuals under ART or
withdrawing from ART and experiencing a rebounding viral
replication. In addition, we detected Nef-specific CD45RA+
IFN-gamma(neg) MIP-1beta+ CD8+ T cells in only 1 out of 10 HIV-1
infected individuals with untreated progressive disease.
Conclusion: The novel antigen-specific CD45RA+ IFN-gamma(neg)
MIP-1beta+ CD8+ T cell population represents a new candidate marker
of long-term natural control of HIV-1 disease progression and a
relevant functional T-cell subset in the evaluation of the immune
responses induced by candidate HIV-1 vaccines.