Induction of TAK (cyclin T1/P-TEFb) in purified resting CD4(+) T lymphocytes by combination of cytokines

Combinations of cytokines are known to reactivate transcription and replica tion of latent human immunodeficiency virus type1I (HIV-1) proviruses in re sting CD4(+) T lymphocytes isolated from infected individuals. Transcriptio n of the HIV-1 provirus by RNA polymerase II is strongly stimulated by the viral Tat protein. Tat function is mediated by a cellular protein kinase kn own as TAK (cyclin T1/P-TEFb) that is composed of Cdk9 and cyclin T1. We ha ve found that treatment of peripheral blood lymphocytes and purified restin g CD4(+) T lymphocytes with the combination of interleukin-2 (IL-2), IL-6, and tumor necrosis factor alpha resulted in an increase in Cdk9 and cyclin T1 protein levels and an increase in TAK enzymatic activity. The cytokine i nduction of TAK in resting CD4(+) T lymphocytes did not appear to require p roliferation of lymphocytes. These results suggest that induction of TAK by cytokines secreted in the microenvironment of lymphoid tissue may be invol ved in the reactivation of HIV-1 in CD4(+) T lymphocytes harboring a latent provirus.