IMMORTALIZATION WITH HERPESVIRUS SAIMIRI MODULATES THE CYTOKINE SECRETION PROFILE OF ESTABLISHED TH1 AND TH2 HUMAN T-CELL CLONES

T blasts of six established human CD4+ T cell clones with defined Ag s pecificity and cytokine secretion profile (3 Th1 and 3 Th2) were immor talized with Herpesvirus saimiri (HVS) and compared with their uninfec ted counterparts for their ability to proliferate, produce cytokines, and express cytolytic activity. HVS-transformed Th1 and Th2 clones nei ther substantially changed their original surface markers nor lose the ir ability to proliferate in response to their specific Ag but did acq uire the ability to proliferate in response to contact signals deliver ed by SRBC or autologous APC alone. In addition, transformation by HVS substantially enhanced the lectin-dependent cytolytic activity of Th1 clones and enabled noncytolytic Th2 clones to exert cytolytic activit y. HVS-transformed Th1 clones but not their uninfected counterparts sp ontaneously transcribed and secreted Th1-type cytokines (IL-2, IFN-gam ma, and TNF-beta) and such a production was further enhanced by stimul ation with either SRBC or PMA plus anti-CD3 mAb. HVS transformed but n ot uninfected Th2 clones constitutively expressed both IL-4 and IL-2 m RNA and secreted IFN-gamma. Stimulation with PMA plus anti-CD3 mAb ind uced uninfected Th2 clones to secrete high amounts of IL-4 and IL-5 bu t not Th1-type cytokines, whereas the same HVS-transformed Th2 showed minimal IL-4 and IL-5 secretion with concomitant high production of IL -2, IFN-gamma, and TNF-beta. Transformation by HVS also resulted in up -regulation of TNF-alpha and IL-3 production by both Th1 and Th2 clone s. The ongoing proliferation of HVS-transformed clones was partially i nhibited by either anti-IL-2 or anti-IL-3 antibodies and virtually abo lished by the combined addition of the two anticytokine antibodies, su ggesting that both IL-2 and IL-3 can function as autocrine growth fact ors for HVS-transformed Th1 and Th2 clones.