Highly avid, oligoclonal, early-differentiated antigen-specific CD8+ T cells in chronic HIV-2 infection

Leligdowicz, A., Onyango, C., Yindom, L.-M., Peng, Y., Cotten, M. , Jaye, A., McMichael, A., Whittle, H., Dong, T. and Rowland-Jones, S. (2010) Highly avid, oligoclonal, early-differentiated antigen-specific CD8+ T cells in chronic HIV-2 infection. European Journal of Immunology, 40(7), pp. 1963-1972. (doi: 10.1002/eji.200940295) (PMID:20411566)

Abstract

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 non‐progressive course of disease. Such responses may be desirable from an HIV vaccine.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Cotten, Professor Matthew
• Authors: Leligdowicz, A., Onyango, C., Yindom, L.-M., Peng, Y., Cotten, M., Jaye, A., McMichael, A., Whittle, H., Dong, T., and Rowland-Jones, S.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity; College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
• Journal Name: European Journal of Immunology
• Publisher: Wiley
• ISSN: 0014-2980
• ISSN (Online): 1521-4141
• Published Online: 21 April 2010