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 costimulation in the T cell-mediated, IFN-gamma-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-gamma and this was independent of the CD40/CD40 ligand interaction. A similar mechanism of IL-12-dependent, CD28/B7 independent production of IFN-gamma 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-gamma 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.
Villegas
E N
EN
Department of Pathobiology, University of Pennsylvania, Philadelphia 19104, USA.
Elloso
M M
MM
Reichmann
G
G
Peach
R
R
Hunter
C A
CA
D000818:Animals; D018122:B7-1 Antigen / Q000502:physiology; D018106:CD28 Antigens / Q000502:physiology*; D002908:Chronic Disease; D005260:Female; D007113:Immunity, Innate; D007117:Immunization, Secondary; D007156:Immunologic Memory / Q000276:immunology*; D018664:Interleukin-12 / Q000502:physiology; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014122:Toxoplasma / Q000276:immunology* / Q000472:pathogenicity; D014124:Toxoplasmosis, Animal / Q000235:genetics / Q000276:immunology* / Q000469:parasitology; D014774:Virulence
D018122:B7-1 Antigen; D018106:CD28 Antigens; D018664:Interleukin-12