Proliferative, IFNgamma and IL-2-producing T-cell responses to HIV-2 in untreated HIV-2 infection.
OBJECTIVE
To evaluate HIV-2-specific proliferative, interferon (IFN)gamma- and interleukin (IL)-2-producing T-cell responses in HIV-2 infection and their relationship with plasma HIV-2 RNA.


METHODS
HIV-2-Gag-p26 and cytomegalovirus (CMV)-specific CD4 T-cell responses from 19 untreated HIV-2-infected subjects (median CD4 cell counts, 561 x 10/l) were compared by lymphoproliferation assay, IFNgamma secretion in culture supernatants by ELISA, and intracellular staining (ICS) of IFNgamma and IL-2. CD8 responses were assessed by IFNgamma-ELISpot using pools of SIVmac239-Gag peptides (87% of homology with HIV-2).


RESULTS
HIV-2-specific IFNgamma production was detected in 53% and 92% patients by ELISA and ICS, respectively, while HIV-2-specific IL-2 production was detected in only 33% by ICS and lymphoproliferation in 21% patients. All IL-2-producing CD4 T cells co-produced IFNgamma. Overall, frequencies of Th1 responses to HIV-2 were similar to CMV in subjects with undetectable plasma HIV-2 RNA, while significantly lower than CMV in HIV-2 RNA-positive subjects, despite similar CD4 cell counts in both groups. In addition, proliferative responses to HIV-2 were correlated to IFNgamma secretion (r > 0.68, P < 0.01), and were significantly higher in HIV-2 RNA-negative (P < 0.05) than in HIV-2 RNA-positive subjects. Frequencies of SIV-Gag-specific CD8 cells, detected in 93% of patients, were also higher in HIV-2 RNA-negative subjects, though not significantly. Overall, HIV-2-specific T-cell responses were not correlated to CD4 cell counts.


CONCLUSIONS
Proliferative, IFNgamma- and IL-2-producing T-cell responses to HIV-2 are as robust as CMV-specific responses in untreated HIV-2 subjects with undetectable plasma HIV-2 levels, independently of CD4 cell depletion and despite lower frequencies of IL-2-producing T cells compared to IFNgamma. In addition, lymphoproliferative responses to HIV-2 were associated with lack of viral replication.
Alatrakchi
Nadia
N
Laboratoire D'Immunologie Cellulaire, INSERM U.543, Hôpital Pitié-Salpêtrière, Paris, France.
Damond
Florence
F
Matheron
Sophie
S
Beretta-Tempelhoff
Sophie
S
Campa
Pauline
P
Carcelain
Guislaine
G
Brun-Vezinet
Françoise
F
Autran
Brigitte
B
D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D015331:Cohort Studies; D003586:Cytomegalovirus Infections / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D015683:Gene Products, gag / Q000276:immunology; D015658:HIV Infections / Q000097:blood / Q000276:immunology*; D015498:HIV-2 / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology*; D007376:Interleukin-2 / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D018655:Lymphocyte Count; D012367:RNA, Viral / Q000097:blood; D013601:T-Lymphocytes / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology
D015683:Gene Products, gag; D007376:Interleukin-2; D012367:RNA, Viral; D007371:Interferon-gamma