IL-4 RAPIDLY PRODUCED BY V-BETA-4 V-ALPHA-8 CD4(-CELLS INSTRUCTS THE DEVELOPMENT AND SUSCEPTIBILITY TO LEISHMANIA-MAJOR IN BALB() T)C MICE/

BALB/c mice develop aberrant T helper 2 (Th2) responses and suffer pro gressive disease after infection with Leishmania major. These outcomes depend on the production of interleukin-4 (IL-4) early after infectio n. Here we demonstrate that the burst of IL-4 mRNA, peaking in drainin g lymph nodes of BALB/c mice 16 hr after infection, occurs within CD4( +) T cells that express V beta 4 V alpha 8 T cell receptors. In contra st to control and V beta 6-deficient BALB/c mice, V beta 4-deficient B ALB/c mice were resistant to infection, demonstrating the role of thes e cells in Th2 development. The early IL-4 response was absent in thes e mice, and T helper 1 responses occurred following infection. Recombi nant LACK antigen from L. major induced comparable IL-4 production in V beta 4 V alpha 8 CD4(+) cells. Thus, the IL-4 required for Th2 devel opment and susceptibility to L. major is produced by a restricted popu lation of V beta 4 V alpha 8 CD4(+) T cells after cognate interaction with a single antigen from this complex organism.