Functional plasticity of the LACK-reactive V beta 4-V alpha 8 CD4(+) T cells normally producing the early IL-4 instructing Th2 cell development and susceptibility to Leishmania major in BALB/c mice

Early production of IL-4 by LACK-reactive V beta4-V alpha8 CD4(+) T cells i nstructs aberrant Th2 cell development and susceptibility to Leishmania maj or in BALB/c mice. This was demonstrated using V beta4(+)-deficient BALB/c mice as a result of chronic infection with MMTV (SIM), a mouse mammary tumo r virus expressing a V beta4-specific superantigen. The early IL-4 response was absent in these mice which develop a Th1 response to L. major. Here, w e studied the functional plasticity of LACK-reactive V beta4-V alpha8 CD4() T cells using BALB/c mice inoculated with L. major shortly after infectio n with MMTV (SIM), i.e. before deletion of V beta4(+) cells. These mice fai l to produce the early IL-4 response to L. major and instead exhibit an IFN -gamma response that occurs within LACK-reactive V beta4-V alpha8 CD4(+) T cells. Neutralization of IFN-gamma restores the production of IL-4 by these cells. These data suggest that the functional properties of LACK-reactive V beta4-V alpha8 CD4(+) T cells are not irreversibly fixed.