Open Journal of Immunology > Vol.4 No.3, September 2014

Meika E. I. Richmond, Sandra A. Kiazyk, Lyle R. McKinnon, Billy Nyanga, Charles Wachihi, Makubo Kimani, Joshua Kimani, Francis A. Plummer, T. Blake Ball

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Centre for the Programme of AIDS Research in South Africa, University of KwaZulu-Natal, Durban, South Africa.
Department of Medical Microbiology, University of Manitoba, Winnipeg, Canada.
Department of Medical Microbiology, University of Nairobi, Nairobi, Kenya.
National Laboratory for HIV Immunology, National Reference Centre for Mycobacteriology, Public Health Agency of Canada, Winnipeg, Canada.

Objectives: The definition of CD8+ T cell attributes that mediate protective immunity in HIV dis-ease progression has not been clearly defined. Although our ability to characterize these cells continues to improve, the extent to which specific memory phenotypic categories of CD8+ T cells reliably represent their functional attributes remains controversial. Methods: We simultaneously assessed surface phenotype and functionality of HIV-specific CD8+ T cells by multiparametric flow cytometry, measuring five CD8+ T cell functions (CD107a, IFNγ, MIP-1β, TNFα and IL2) and phenotypic markers CCR7, CD45RA, and CD27, in parallel in 24 HIV-infected individuals. Results: Virus-specific responses were contained within all eight phenotypic categories defined using CCR7, CD45RA, and CD27. Phenotypic profiles of HIV-specific cells differed from CEF-specific cells, with HIV-specific cells having higher levels of CD45RA (p = 0.008). Interestingly a large portion of CEF and HIV-specific cells were found within previously undefined phenotypes CCR7+CD27－CD45RA+ (14.6% and 17.2%, respectively) and CCR7+CD27－CD45RA－(14.8% and 15.8%, respectively). In addition, up to 10% - 20% of responding cells were phenotypically “naive”. Additionally, memory phenotypes of cells exhibiting monofunctional and polyfunctional responses frequently differed, and failed to associate with a consistent phenotype representing functionally active cells. Conclusion: These data suggest that particularly after antigen stimulation, that surface phenotypes defined by CCR7, CD27 and CD45RA expression on antigen-specific CD8+ T cells, reflect a wide range of immunological functions, and that no single phenotype defined by memory marker expression can reliably be used to identify functional capacity.

CD8+T Cells, HIV, Memory Phenotype, Polyfunctionality, Disease Progression

Richmond, M. , Kiazyk, S. , McKinnon, L. , Nyanga, B. , Wachihi, C. , Kimani, M. , Kimani, J. , Plummer, F. and Blake Ball, T. (2014) Memory Phenotypes of HIV-Specific CD8+ T Cell Responses Are Independent of Functional Activity as Defined by Cytokine Output. Open Journal of Immunology, 4, 83-95. doi: 10.4236/oji.2014.43012.