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Detection of high frequencies of HIV-1 cross-subtype reactive CD8 T lymphocytes in the peripheral blood of HIV-1-infected Kenyans

Currier, Jeffrey Ra; Dowling, William Ea; Wasunna, K Moniqueb; Alam, Uzmac; Mason, Carl Jc; Robb, Merlin La; Carr, Jean Ka; McCutchan, Francine Ea; Birx, Deborah La; Cox, Josephine Ha

Basic Science

Objectives: To quantitate rapidly the frequency of HIV-1 subtype-specific and broadly HIV-1 cross-subtype-reactive CD8 T cells in the peripheral blood of HIV-1-infected individuals from a geographical region of multiple subtype endemicity.

Methods: Autologous B-lymphoblastoid cell lines infected with recombinant vaccinia-viruses expressing gag, env and nef gene products from HIV-1 subtypes A–H were used as antigen-presenting cells to stimulate CD8 T cells from cryopreserved peripheral blood mononuclear cells. Cross-subtype and subtype-specific CD8 cell responses were assessed by flow cytometry for the upregulation of IFN-γ gene expression in specifically activated CD8 T cells.

Results: Strikingly high frequencies of circulating CD8 T cells (up to 11.3% of peripheral CD8 T cells) with specificity for HIV-1 were detectable using this methodology. Both subtype-specific and broadly cross-subtype-reactive CD8 T cells were detected as assessed by IFN-γ production after stimulation. The pattern of cross-subtype reactivity appeared to be random when the results were assessed as a population, but analysis of the full-length sequence of the infecting virus for each individual showed some skewing of the CD8 cell response towards the infecting subtype.

Conclusion: High frequencies of HIV-1 cross-subtype-reactive peripheral CD8 T cells can be detected in individuals from a multiple subtype endemic region, providing an incentive for vaccine advancement in such locations. The future assessment of the subtype specificity of cellular immune responses requires full-length sequencing of the infecting virus in conjunction with a comprehensive analysis of phenotypic and functional parameters.

From the aUS Military HIV Research Program, Suite 200, 13 Taft Court, Rockville, MD 20850, USA; b Centre for Clinical Research, Kenya Medical Research Institute, Nairobi, Kenya; and cUS Army Medical Research Unit, Nairobi, Kenya.

Correspondence to: Jeffrey R. Currier, The US Military HIV Research Program, Suite 200, 13 Taft Court, Rockville, MD 20850, USA. Tel: +1 301 251 8311; fax: +1 301 762 4177; e-mail: jcurrier@hivresearch.org

Received: 24 October 2002; revised: 27 February 2003; accepted: 11 March 2003.

© 2003 Lippincott Williams & Wilkins, Inc.