CD28 is required for T cell activation and IFN-gamma production by CD4+ and CD8+ T cells in response to Trypanosoma cruzi infection.
In the present study we evaluated the mechanisms behind the implication of the costimulatory molecule CD28 for the immune response against the intracellular protozoan parasite Trypanosma cruzi. Our results reveal a critical role for CD28 in the activation of both CD4+ and CD8+ T cells and induction of the effector mechanisms that ultimately mediate the control of parasite growth and pathogenesis in infected mice. CD28-deficient (CD28-/-) mice are highly susceptible to T. cruzi infection, presenting higher parasitemia and tissue parasitism, but less inflammatory cell infiltrate in the heart than C57Bl/6 wild-type (WT) mice. All the infected WT mice survived acute infection, whereas 100% of CD28-/- mice succumbed to it. The increased susceptibility of the CD28-/- mice was associated with a dramatic decrease in the production of IFN-gamma by both CD4+ and CD8+ T cells resulting in a diminished capacity to produce nitric oxide (NO) and mediate parasite killing. T cell activation was also profoundly impaired in CD28-/- mice, which presented decreased lymphoproliferative response after the infection compared to WT mice. Together, these data represent the first evidence that CD28 is critical for efficient CD4+ T cell activation in response to T. cruzi infection in mice.
Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, Avenida Professor Lineu Prestes, 1530 São Paulo, SP 05508-900, Brazil. martinso@mail.med.upenn.edu
Gislâine Aparecida
GA
Martins
Ana Paula
AP
Campanelli
Roberta Borges
RB
Silva
Carlos Eduardo
CE
Tadokoro
Momtchilo
M
Russo
Fernando Queiroz
FQ
Cunha
Luiz Vicente
LV
Rizzo
João Santana
JS
Silva
D000818:Animals; D018106:CD28 Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D014355:Chagas Disease / Q000276:immunology* / Q000469:parasitology; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis*; D016753:Interleukin-10 / Q000032:analysis; D018664:Interleukin-12 / Q000276:immunology; D015847:Interleukin-4 / Q000032:analysis; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009206:Myocardium / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D018512:Parasitemia; D014349:Trypanosoma cruzi / Q000276:immunology*
D018106:CD28 Antigens; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; D009569:Nitric Oxide; D007371:Interferon-gamma