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*
Department of Pathobiology, University of Pennsylvania, Philadelphia, PA 19104; and
Bristol Myers Squibb Pharmacology Research Institute, Princeton, NJ 08543
CD28 deficient (CD28-/-) mice were used to study the
role of costimulation in the T cell-mediated, IFN-
-dependent
mechanism of resistance to Toxoplasma gondii. These mice
were resistant to infection with the ME49 strain 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- and this was independent of the CD40/CD40 ligand
interaction. A similar mechanism of IL-12-dependent, CD28/B7
independent production of IFN- by T cells was also observed in
wild-type mice. Interestingly, although chronically infected wild-type
mice were resistant to rechallenge with the virulent RH strain of
T. gondii, chronically infected CD28-/-
mice were susceptible to rechallenge with the RH strain. This
deficiency in the protective memory response by CD28-/-
mice correlated with a lack of IL-2 and IFN- in recall responses and
reduced numbers of CD4+ T cells expressing a memory
phenotype. Together, our findings demonstrate that CD28 is not required
for the development of a protective T cell response to T.
gondii, but CD28 is required for an optimal secondary immune
response.
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