CTLA4 (CD152) modulates the Th subset response and alters the course of experimental Leishmania major infection

Since both the nature and the amplitude of an antigen‐specific T cell response are dependent on co‐stimulatory signals, we have invesigated the role of CD28 / CD152‐mediated T cell co‐stimulation in the regulation of experimental cutaneous leishmaniasis. CD28‐deficient mice and their wild‐type littermates are equally susceptible to Leishmania major infection. Whole anti‐CD152 antibody significantly exacerbates the disease while anti‐CD152 Fab ameliorates the disease in genetically susceptible BALB / c mice but not in C57BL / 6, a resistant strain. The anti‐CD152‐induced exacerbation of the disease is accompanied by increased IL‐4‐secreting cell number, diminished parasite‐specific delayed‐type hypersensitivity (DTH) response and augmented anti‐2,4,6‐trinitrophenyl (TNP) IgG1 in response to TNP‐leishmanial antigen crude soluble antigen (CSA), suggesting an exaggerated Th2 type of response. Anti‐CD152 Fab‐mediated amelioration of the disease is associated with increased IFN‐γ‐secreting cell number, increased parasite‐specific DTH response and enhanced IgG2a isotype in response to TNP‐CSA suggesting a Th1 type of response. Unlike TNP‐CSA, TNP‐keyhole limpet hemocyanin does not induce the change in Ig isotype, indicating that the immunomodulatory effect of anti‐CD152 is antigen specific. Anti‐CD152 antibody‐induced early change in Th subsets suggests an important role for CD152 in determining the course of L. major infection, perhaps by alteration of Th subset differentiation.