Role of CD28 in the generation of effector and memory responses required for resistance to Toxoplasma gondii

CD28 deficient (CD28(-/-)) mice were used to study the role of costimulatio n in the T cell-mediated, IFN-gamma-dependent mechanism of resistance to To xoplasma gondii, These mice were resistant to infection with the ME49 strai n of T, gondii, Analysis of the immune response of acutely infected CD28(-/ -) mice revealed that IL-12 was required for T cell production of IFN-gamma and this was independent of the CD40/CD40 ligand interaction. A similar me chanism of IL-12-dependent, CD28/B7 independent production of IFN-gamma by T cells was also observed in wild-type mice, Interestingly, although chroni cally infected wild-type mice were resistant to rechallenge with the virule nt RH strain of T,gondii, chronically infected CD28(-/-) mice were suscepti ble to rechallenge with the RH strain, This deficiency in the protective me mory response by CD28(-/-) mice correlated with a lack of IL-2 and IFN-gamm a in recall responses and reduced numbers of CD4(+) T cells expressing a me mory phenotype, Together, our findings demonstrate that CD28 is -not requir ed for the development of a protective T cell response to T, gondii, but CD 28 is required for an optimal secondary immune response.