![]() The x-axis numbers represent days post-Ontak administration. ( B) Absolute numbers (per milliliter) of the aggregated Gag- and Env-specific CD4 + and CD8 + T cells at different time points following the first round of Ontak administration. The color scheme represents the number of cytokines produced by the SIV-specific T cells, and their proportion is illustrated as color-coded ring surrounding the pie charts. The pie charts depict functionality based on the combination of cytokines expressed. Absolute numbers of CD8 + T cells/ml for each time point are marked beneath each pie graph. Cytokines tested for include the following: TNF-α (T), IL-2 (2), IFN-γ (I), CD107α (7), and MIP-1β (M). ( A) Serial monitoring of SIV-specific T cell polyfunctionality after the first round of Ontak administration was achieved by stimulating PBMCs with Gag SIVsab92018 peptide pools, followed by intracellular cytokine staining. Ontak administration boosted the overall CTL responses in SIVsab-infected controller RMs. It is thus conceivable that Treg depletion in HIV/SIV subjects may improve cell-mediated immunity Materials and Methods Altogether, these observations support a major involvement of Tregs in suppressing the protective effector immune responses against HIV. Furthermore, Treg depletion resulted in a significant improvement of cellular immune responses and prolonged survival in cancer patients with T lymphomas ( 9). ![]() Inhibition of cellular immune responses by Tregs was also reported in other infectious and noninfectious conditions, such as hepatitis C and several types of cancer ( 9). During chronic HIV/SIV infection, Tregs contribute to the impairment of CTL responses, as suggested by the following observations: Treg expansion correlates with loss of CTL function ( 12– 14) ex vivo Treg depletion from blood and lymph nodes enhances T cell responses to HIV or SIV Ags ( 9) HIV nonprogressors have a high perforin/FOXP3 ratio and HLA B27 + and B57 + HIV-specific CD8 + T cells from elite controllers are able to evade Treg suppression ( 15, 16). During the acute HIV/SIV infection, Tregs may decisively contribute to the rapid establishment of the HIV reservoir by reversing the immune activation status of CD4 + T cells ( 9). Furthermore, through their regulatory function, Tregs can indirectly shape the reservoir.
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