Memory Phenotypes of HIV-Specific CD8+ T Cell Responses Are Independent of Functional Activity as Defined by Cytokine Output

Abstract

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.

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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.

Conflicts of Interest

The authors declare no conflicts of interest.

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