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A DIRECT LINK BETWEEN LOSS OF T-CELL FUNCTION AND DOWNREGULATION OF TCRΖ EXPRESSION IN CHRONIC VIRAL INFECTIONS?

Abstract:

Methods: PBMC from healthy and HIV-infected individuals were stimulated with either TCR-bypassing or TCR dependent mitogens. Both magnitude and polyfunctionality of the responding T cells and their TCRζ expression levels were determined by intracellular measurement of IFNγ, IL-2, TNFα and MIP1β and TCRζ. Results: The magnitude and polyfunctionality of CD8+ T cells positively correlated with TCRζ expression levels, in both healthy and HIV-infected individuals. CD8+ T cells producing IL-2 alone or a combination of IL-2 and MIP1β consistently exhibited low TCRζ expression levels, in all individuals. However, in HIV infected individuals, low TCRζ levels extended to all CD8+ T cells producing IL-2. Conclusion: Here we demonstrated, on a cellular basis, the direct correlation between polyfunctionality and magnitude of cytokine production in CD8+ T cells and TCRζ expression level, both in healthy and HIV-infected individuals.