ACTIVATION-MEDIATED CD4(-CELL UNRESPONSIVENESS DURING ACUTE TOXOPLASMA-GONDII INFECTION IN MICE() T)

Infection of mice with Toxoplasma gondii has been shown to induce a tr ansient state of immune down-regulation. Earlier reports have demonstr ated the role of cytokines, in particular IL-10, in this host response , Here evidence is presented that T. gondii, a major opportunistic pat hogen of the newborn and those with AIDS, is able to induce CD4(+) T c ell apoptosis in the infected murine host, We have examined the change s in the CD4(+) T cell population that occur during acute infection in an experimental mouse model, Seventy-six percent of the CD4(+) T cell population increased in volume by day 7 post-infection and expressed T cell maturation markers (CD44(hi), IL-2R(hi), Mel-14(lo)), Further n oted was a clonal activation of several CD4(+) T cells subsets express ing the V-beta chain of the TCR, At day 7 post-infection, partial redu ction of all CD4(+) T cells to mitogen or parasite antigen stimulation was observed, in particular V(beta)5 T cells, Addition of rIL-2 parti ally restored the CD4(+) T cell proliferative response in vitro, The T cell activation marker CTLA-4 could not be detected and the co-stimul atory molecule, CD28, was down-regulated, Electrophoretic and morpholo gic analysis of these cells post-culture demonstrated a DNA fragmentat ion pattern and cell death consistent with apoptosis, These studies de monstrate for the first time in a protozoan parasite that activation-i nduced CD4(+) T cell unresponsiveness occurs during acute 7: gondii in fection in mice, and may be important in immune down-regulation and pa rasite persistence in the infected host.