AN IN-VITRO MODEL FOR INFECTION WITH LEISHMANIA-MAJOR THAT MIMICS THEIMMUNE-RESPONSE IN MICE

By using a primary in vitro response specific for Leishmania major, no rmal T cells from resistant CBA/ CaH-T6J and susceptible BALB/c mice c ommit to a Th1 and a Th2 response, respectively. Since commitment occu rred, we measured the production of gamma interferon (IFN-gamma), inte rleukin-1 (IL-1), IL-2, IL-4, IL-5, IL-10, and IL-12, prostaglandin E- 2 (PGE(2)), transforming growth factor beta (TGF-beta), and nitric oxi de in the first 7 days of the response to identify factors that are cr itical for Th1 and Th2 development. While cells from resistant CBA mic e produced more IFN-gamma, IL-10, and nitric oxide, cells from suscept ible BALB/c mice produced more IL-1 alpha, IL-5, PGE(2), and TGF-beta. Although substantial amounts of IL-12 were detected, IL-12 did not as sociate with either Th1 or Th2 development. We did not anticipate that cells from resistant CBA mice would make more IL-10 in vitro. However , this also occurred in vivo since CBA mice produced substantial amoun ts of IL-10 following infection with L. major. Moreover, adding anti-I L-10 to primary in vitro responses enhanced production of IFN-gamma an d nitric oxide by cells from CBA and BALB/c mice. Therefore, IL-10 can not be regarded as a cytokine that associates with susceptibility to i nfection with L. major. Finally, the data presented here suggest that a collection of factors that can be produced by accessory cells influe nce Th commitment (e.g., IL-1, PGE(2), and TGF-beta favor Th2 developm ent).