DISEASE SUSCEPTIBILITY AND DEVELOPMENT OF THE CYTOKINE REPERTOIRE IN THE MURINE LEISHMANIA-MAJOR MODEL

The marine Leishmania major model has proven fertile ground for the el ucidation of CD4+ T cell effector subset differentiation in vivo. The availability of a highly susceptible inbred strain, BALB/c, that devel ops progressive disease due to the aberrant differentiation of Th2, as opposed to protective Th1, responses, has allowed the identification of both T cell intrinsic as well as T cell extrinsic properties that c ombine to mediate disease outcome, The intrinsic T cell phenotype rela tes to the capacity of BALB/c-derived CD4+ T cells to acquire the pote ntial to secrete IL-4 more readily than cells from other strains of mi ce. The extrinsic T cell phenotype relates to the creation of a T cell repertoire capable of recognizing the immunodominant parasite antigen , Together, the two traits confer the aberrant response seen in suscep tible mice challenged with L. major.