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IMPACT OF PREGNANCY ON THE MAGNITUDE AND BREADTH OF ANTIGEN RECOGNITION BY HIV-SPECIFIC CYTOTOXIC T LYMPHOCYTES
E Jolette, D Ransy, J Samson, M Caty, S Valois, N Lapointe, M Boucher, H Soudeyns
Objectives: Characterization of HIV-specific cytotoxic T lymphocytes (CTL) responses during pregnancy will facilitate the design of optimal strategies to prevent mother-to-child transmission (MTCT) of HIV-1. Our objective is to define the influence of initiation and progression of pregnancy on the magnitude and breadth of antigen recognition by HIV-specific CTL.
Methods: Study subjects were women infected with B or non-B HIV-1 subtypes who had one or two consecutive pregnancies (n=15). All subjects were treated with combinations of antiretroviral agents for maternal health and to prevent MTCT. Antigenic specificity of CTL was evaluated on serially-obtained (pre-pregnancy, 1st, 2nd, 3d trimesters and post-partum) CD4-depleted samples of peripheral blood mononuclear cells using IFN-gamma ELISpot using overlapping peptides corresponding to Gag sequences from HIV-1 clades A, B, C and D.
Results: Longitudinal changes in CTL responses were observed in terms of overall magnitude, which ranged between 160 and 20,000 spot-forming units (SFU)/million cells and at the level of breadth of antigen recognition, with 2-12 peptide pools generating CTL reactivity. Magnitude and breadth of antigen recognition by HIV-specific CTL were significantly higher in subjects with detectable viral load, as compared with subjects in whom viral load was undetectable. Moreover, our results revealed for the first time that initiation of pregnancy by itself has little influence on the magnitude of CTL responses in terms of IFN-gamma production.
Conclusions: Longitudinal variations in terms of magnitude and breadth of antigen recognition could be explained by sequential waves of expansion and contraction of CTL clones of mixed antigenic specificity and/or by continuing viral escape from CTL responses. These results support the fact that HIV-infected women maintain immunocompetence throughout gestation, at least in the context of effective antiretroviral treatment. Taken together, these observations may help to promote maternal immunization as a strategy to prevent MTCT of HIV-1.