Dissociated Production of Perforin, Granzyme B, and IFN-γ by HIV-Specific CD8Cells in HIV Infection.

Autor: Stefanie Kuerten, Tobias M. Nowacki, Thomas O. Kleen, Robert J. Asaad, Paul V. Lehmann, Magdalena Tary-Lehmann
Zdroj: AIDS Research & Human Retroviruses; Jan2008, Vol. 24 Issue 1, p62-71, 10p
Abstrakt: CD8T cells play a crucial role in the control of viral infections such as HIV. The functional characterization of HIV-specific CD8T cells has so far been largely restricted to studies of IFN-γ. The TCR-triggered release of the effector molecules perforin (PFN) and granzyme B (GzB), however, is thought to be a central pathway for the destruction of virus-infected target cells by CD8effector T cells. Here we would like to address two major findings. On the one hand we propose that ex vivomeasurements of PFN and GzB secretion via ELISPOT may permit the distinction between in vivoresting versus activated CD8memory T cells in healthy and HIV-infected individuals. Therefore, extending the present standard of IFN-γ measurements to the analysis of PFN and GzB release in functional T cell assays will provide new insights into CD8effector T cell functions. It should enable the evaluation of therapeutic vaccination efficacy by its ability to reactivate and convert IFN-γ-positive, but GzB- and PFN-negative memory CD8T cells into PFNGzB-secreting effector cells. On the other hand, we report on a frequent ex vivodissociation of the HIV peptide-induced secretion of PFN and GzB in chronic HIV infection underlining CD8effector T cell diversity in this disease––an aspect that also has to be accounted for in immune monitoring approaches. [ABSTRACT FROM AUTHOR]
Databáze: Supplemental Index