HIV type 1 antigen-responsive CD4+ T-lymphocytes in exposed yet HIV Type 1 seronegative Ugandans.
CD4(+) T cell help is important for the functionality of CD8(+) cytotoxic T-lymphocytes (CTLs) in limiting viral replication and may contribute to mediation of apparent resistance to HIV-1 infection in exposed seronegative (ESN) individuals. Using five HIV-1 antigens in an intracellular cytokine assay, the presence of specific antigen-responsive interferon- gamma-positive (IFN-gamma(+)) CD69(+) CD4(+) T-lymphocytes was evaluated in ESNs, their seropositive partners, and unexposed seronegative controls. Ten ESNs (five females, five uncircumcised males) were identified from 10 HIV-1 serodiscordant couples with a history of frequent unprotected sexual intercourse. All ESNs and controls were negative on two EIAs and for HIV-1 proviral DNA. The frequency of ESNs with antigen-responsive IFN-gamma(+) CD69(+) CD4(+) T-lymphocytes ranged from three to five of eight for the different HIV-1 antigens. Six of eight ESNs tested had a positive response to at least one of the five antigens. Responses were on average 3.5 times higher among seropositives compared to ESNs and absent in the five unexposed controls. A negative correlation was noted between responses in ESNs and the plasma viral load of their seropositive spouse. Clade-specific and cross-clade reactivity were noted in both ESNs and seropositive partners tested. The findings confirm that ESNs are in a state of HIV-1-specific immune activation and suggest that HIV-1-specific IFN-gamma(+) CD69(+) CD4(+) T-lymphocytes in addition to HIV-1-specific CD8(+) CTLs already described by others are potential immunological correlates of protection from persistent HIV-1 infection.
Medical Research Council's Programme on AIDS in Uganda, UVRI, Entebbe, Uganda.
Anthony
A
Kebba
Pontiano
P
Kaleebu
Jennifer
J
Serwanga
Samantha
S
Rowland
David
D
Yirrell
Robert
R
Downing
Jill
J
Gilmour
Nesrina
N
Imami
Frances
F
Gotch
Jimmy
J
Whitworth
D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D015488:HIV Antigens / Q000276:immunology*; D018023:HIV Seronegativity / Q000276:immunology*; D006679:HIV Seropositivity / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D037181:Lectins, C-Type; D008297:Male; D018454:Spouses; D014454:Uganda; D019562:Viral Load; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D015488:HIV Antigens; D007371:Interferon-gamma; D037181:Lectins, C-Type; D000099192:CD69 Antigens