INDUCTION OF A TH2 POPULATION FROM A POLARIZED LEISHMANIA-SPECIFIC TH1 POPULATION BY IN-VITRO CULTURE WITH IL-4

The infection of mice with Leishmania major parasite induces polarized Th1 and Th2 responses that cannot be significantly changed in vivo af ter 2 to 3 wk of infection by using either cytokines or anti-cytokine Abs. It is not clear, however, whether the T cell populations are irre versibly differentiated or whether the inability to modify the cytokin e production reflects inefficiencies in the experimental treatments or complications of the infection itself. To study this further, we have cultured CD4(+) T cells from L. major-infected mice with specific Ag, APC, and IL-2, in the presence or absence of different cytokines and/ or anti-cytokine Abs. Th1 cells cultured for 1 wk in the presence of I L-4 produced very low levels of IFN-gamma but, instead, produced high levels of IL-4 and IL-10, suggesting that IL-4 was able to cause the c onversion of a Th1 into a Th2 population. The Th2-like population gene rated in vitro was stable and retained its phenotype in vivo when tran sferred into L. major-infected C.B-17 scid mice. In contrast, the pres ence of IFN-gamma and IL-12 during the Th2 cell stimulation enhanced I FN-gamma production but was not sufficient to induce a complete conver sion of a Th2 into a Th1-like population, Taken together, these data s how that highly polarized murine Th populations can be modified and ev en converted to the opposite cytokine phenotype in vitro, suggesting p ossible therapeutic applications for cytokines.