InBALB/c mice, IL-4 production during the initial phase of infection with Leishmania major is necessary and sufficient to instruct Th2 cell development resulting in progressive disease

contrast to intact BALB/c mice, BALB/c mice rendered deficient in V beta 4( +) CD4(+) T cells develop a Th1 response to infection with Leishmania major and are resistant. V beta 4-deficient BALB/c mice are unable to generate t he early IL-4 transcription occurring in V beta 4 V alpha 8 CD4(+) T cells of BALB/c mice within 1 day of infection. Here we demonstrate that treatmen t of V beta 4-deficient BALB/c mice with IL-4 during the first 64 h after i nfection instructs Th2 cell development and susceptibility to infection. Th e demonstrated inability of IL-4 to reverse the resistant phenotype of BALB /c mice treated with anti-CD4 mAb the day before infection suggest that the se effects of IL-4 require its interaction,vith CD4(+) T cells. In contrast to draining lymph node cells from BALB/c mice, cells from V beta 4-deficie nt BALB/c mice remain responsive to IL-12 following infection. Strikingly, administration of IL-4 to V beta 4-deficient BALB/c mice renders their lymp h node cells unresponsive to IL-12 by down-regulating IL-12R beta 2-chain e xpression. This study directly demonstrates that in BALB/c mice IL-4 is nec essary and sufficient to initiate the molecular events steering Th2 cell ma turation and susceptibility to L. major.