Suppression of the human immunodeficiency virus long terminal repeat by CD8(+) T cells is dependent on the NFAT-1 element

CD8(+) T lymphocytes of HIV-1 infected individuals produce a soluble factor that efficiently suppresses HIV-1 replication at the transcriptional level, We show here that the response of the HIV-1 long terminal repeat (LTR) to mitogenic or Tat-mediated activation is sensitive to the suppressive action of a Herpesvirus saimiri (HVS)-transformed CD8(+) T cell clone from an HIV-infected individual and supernatants from CD8(+) T cells of HIV-1-infected asymptomatic subjects (CD4(+) > 350/mu l). Mutagenesis of NF kappa B or Sp-l elements within the LTR resulted in no change in the ability of CD8(+) T cell supernatants to inhibit Tat- or mitogen-mediated LTR transcription, However, the response to HIV-1 Tat by a LTR in which the interleukin (IL)-2 homology NFAT-1 region was mutated resulted in almost complete elimination of suppression by CD8(+) T cells, This was not observed when the NFAT-1 mutant LTR was activated by mitogen, We have previously shown that gene expression directed by the HIV-1 NF kappa B elements is inhibited by CD8(+) cell-derived supernatants (Copeland ct al., AIDS Res Hum Retroviruses, 1995;11:1321-1326). Taken together, these observations suggest that mitogenic activation, mediated primarily through the NF kappa B enhancer, is susceptible to CDS-mediated inhibition, however, inhibition of Tat-mediated activation may rely upon a different pathway that is NFAT-1 dependent.