Highly avid, oligoclonal, early-differentiated antigen-specific CD8<sup>+</sup>T cells in chronic HIV-2 infection
Leligdowicz A., Onyango C., Yindom LM., Peng YC., Cotten M., Jaye A., McMichael A., Whittle H., Dong T., Rowland-Jones S.
HIV-1-specific CD8+T cells are present in most HIV-1-infected people and play an important role in controlling viral replication, but the characteristics of an effective HIV-specific T-cell response are largely unknown. The majority of HIV-2-infected people behave as long-term non-progressors while those who progress to AIDS do so in a manner indistinguishable from HIV-1. A detailed study of HIV-2 infection may identify protective immune responses. Robust gag p26-specific T-cell responses are elicited during HIV-2 infection and correlate with control of viremia. In this study, we analyzed features of an HLA-B*3501-restricted T-cell response to HIV-2 p26 that may contribute to virus control. In contrast to HIV-1, HIV-2-specific T cells are at an early stage of differentiation (CD27+CD28+), a finding that relates directly to CD4+T-cell levels and inversely to immune activation. The cells demonstrate IFN-γ secretion, oligoclonal T-cell receptor Vβ gene segment usage, exceptional avidity and secretion of pro-inflammatory cytokines. Despite the potentially strong selection pressure imposed on the virus by these cells, there was no evidence of HIV-2 sequence evolution. We propose that in chronic HIV-2 infection, the maintenance of early-differentiated, highly avid CD8+T cells could account for the nonprogressive course of disease. Such responses may be desirable from an HIV vaccine. © 2010 Wiley-VCH Verlag GmbH & Co. KGaA.