|
14th International AIDS ConferenceBarcelona, Spain — July 7-12, 2002 |
Int Conf AIDS. 2002 Jul 7-12;14:Abstract No. MoOrA1055
BACKGROUND: 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 resistance to HIV-1 infection in ESNs. The presence of HIV-1-specific CD4+ Helper T lymphocyte (HTL) responses in ESNs would therefore suggest their elicitation should be one of the objectives of AIDS vaccine strategies.
METHODS: 15 ESNs (8 females, 7 uncircumcised males) were identified from 15 HIV-1 sero-discordant couples with a history of frequent unprotected sexual intercourse and evaluated for the presence of HIV-1-specfic interferon-gamma+ (IFN-γ+) CD69+ CD4+ HTL responses to 5 HIV-1 antigens (clade A/G Remune, clade B gag p24, gp120 V3 loop peptides from clades A, B and D) using an intracellular cytokine assay. Such analysis was also performed in sero-positive (SP) partners, their viral load (VL) determined by the Roche assay and virus subtyped by sequencing in env V3, gag p17 and p24 regions.
RESULTS: All 15 ESNs were negative on two ELISAs and for HIV-1 proviral DNA. The frequency of ESNs with positive IFN-γ+ CD69+ CD4+ HTLs ranged from 3/8 to 4/8 for the different antigens. 6/8 tested had a positive response to at least one antigen. Responses were on average 3.5 times higher among SPs compared to ESNs and absent in unexposed sero-negative controls. A negative correlation was noted between responses in ESNs and the pVL of their SP spouse. Clade specific and cross-clade reactivity were noted in both ESNs and SPs.
CONCLUSIONS: Findings confirm that ESNs are in a state of HIV-1-specific immune activation and support our hypothesis that, in addition to HIV-1-specific CD8+ CTL responses already described in other studies, HIV-1-specific IFN-γ+ CD69+ CD4+ HTL responses are also present and may contribute to the mediation of resistance in ESNs. Though responses were quantitatively higher in SPs, qualitative differences may account for their contribution to resistance in ESNs.
Presenting author: Anthony Kebba
1Medical Research Council's Programme on AIDS in Uganda, Uganda Virus Research Institute, Medical Research Council's Programme on AIDS in Uganda, Uganda Virus Research Institute, P. O. Box 49, Entebbe, Uganda.
2Imperial College of Science, Technology and Medicine, department of Immunology, Chelsea & Westminster Hospital, London, United Kingdom.
3Center for HIV Research, University of Edinburgh, Edinburgh, United Kingdom.
020708
MoOrA1055
Copyright © 2002 - International AIDS Society (IAS). Reproduction of this abstract (other than one copy for personal reference) must be cleared through the IAS.
