Functional plasticity of the LACK-reactive Vβ4-Vα8 CD4+ T cells normally producing the early IL-4 instructing Th2 cell development and susceptibility to Leishmania major in BALB/c mice

Abstract

Early production of IL-4 by LACK-reactive Vβ4-Vα8 CD4+ T cells instructs aberrant Th2 cell development and susceptibility to Leishmania major in BALB/c mice. This was demonstrated using Vβ4+-deficient BALB/c mice as a result of chronic infection with MMTV (SIM), a mouse mammary tumor virus expressing a Vβ4-specific superantigen. The early IL-4 response was absent in these mice which develop a Th1 response to L. major. Here, we studied the functional plasticity of LACK-reactive Vβ4-Vα8 CD4+ T cells using BALB/c mice inoculated with L. major shortly after infection with MMTV (SIM), i. e. before deletion of Vβ4+ cells. These mice fail to produce the early IL-4 response to L. major and instead exhibit an IFN-γ response that occurs within LACK-reactive Vβ4-Vα8 CD4+ T cells. Neutralization of IFN-γ restores the production of IL-4 by these cells. These data suggest that the functional properties of LACK-reactive Vβ4-Vα8 CD4+ T cells are not irreversibly fixed.