IL-4 rapidly produced by V beta 4 V alpha 8 CD4+ T cells instructs Th2 development and susceptibility to Leishmania major in BALB/c mice

Immunity. 1997 May;6(5):541-9. doi: 10.1016/s1074-7613(00)80342-8.


BALB/c mice develop aberrant T helper 2 (Th2) responses and suffer progressive disease after infection with Leishmania major. These outcomes depend on the production of interleukin-4 (IL-4) early after infection. Here we demonstrate that the burst of IL-4 mRNA, peaking in draining 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 contrast to control and V beta 6-deficient BALB/c mice, V beta 4-deficient BALB/c mice were resistant to infection, demonstrating the role of these cells in Th2 development. The early IL-4 response was absent in these mice, and T helper 1 responses occurred following infection. Recombinant 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 development and susceptibility to L. major is produced by a restricted population of V beta 4 V alpha 8 CD4+ T cells after cognate interaction with a single antigen from this complex organism.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, Protozoan / pharmacology
  • CD4 Antigens / analysis*
  • CD4 Antigens / genetics
  • Cell Differentiation / immunology
  • Disease Susceptibility
  • Female
  • Immunity, Innate
  • Interleukin-4 / biosynthesis*
  • Interleukin-4 / genetics
  • Leishmania major / immunology*
  • Leishmaniasis, Cutaneous / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Protozoan Proteins / pharmacology
  • RNA, Messenger / biosynthesis
  • Receptors, Antigen, T-Cell, alpha-beta / immunology*
  • Receptors, Antigen, T-Cell, alpha-beta / metabolism
  • Recombinant Proteins / pharmacology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism*
  • Th2 Cells / cytology*


  • Antigens, Protozoan
  • CD4 Antigens
  • Protozoan Proteins
  • RNA, Messenger
  • Receptors, Antigen, T-Cell, alpha-beta
  • Recombinant Proteins
  • LACK antigen, Leishmania
  • Interleukin-4