Mechanism of HIV-1 Tat induced inhibition of antigen-specific T cell responsiveness.

摘要: HIV-1 Tat has been shown to have an inhibitory effect on the Ag-specific responsiveness of human peripheral T cells. We previously demonstrated that this retroviral protein binds and partially inhibits enzymatic activity dipeptidyl aminopeptidase type IV (DP IV), also known as CD26, which is expressed a variety mammalian tissue, including lymphocytes. A number studies implicated role for DP in activation By utilizing Tat, well ProboroPro, potent specific boronic acid analog inhibitor IV, we show here blocking inactivates Ag anti-CD3-mediated cell proliferation. Neither mitogen nor anti-CD2 mediated proliferation lymphocytes, however, impaired by IV. The target molecule inhibition induced both compounds was confirmed finding soluble neutralized reduced responsiveness. could be overcome addition exogenous IL-2, suggesting or inactivation results state anergy, probably interfering with delivery amplification signal necessary IL-2 production. This further substantiated costimulation PBMC via CD28 molecule, initiates non-TCR-dependent signaling pathway, overcomes ProboroPro. fact ProboroPro no impact stimulation cells PMA ionomycin implies influencing events before kinase C Ca2+ flux. These suggest signals generated engagement TCR-CD3 complex nominal Ag.