title: Role of CD28 in polyclonal and specific T and B cell responses required for protection against blood stage malaria.
abstract: The role of B7/CD28 costimulatory pathway in the polyclonal and specific lymphocyte activation induced by blood stages of Plasmodium chabaudi AS was investigated in CD28 gene knockout (CD28(-/-)) and C57BL/6 (CD28(+/+)) mice. Analysis of the spleen during the acute infection revealed a similar increase in T and B cell populations in both groups of mice. Moreover, CD28(-/-) mice were able to develop a polyclonal IgM response to P. chabaudi. On the contrary, the polyclonal IgG2a response was markedly reduced in the absence of CD28. Production of IFN-gamma; up-regulation of CD69, CD40L, CD95 (Fas), and CD95L (Fas ligand); and induction of apoptosis were also affected by the lack of CD28. Interestingly, the ability to control the first parasitemia peak was not compromised in acutely infected CD28(-/-) mice, but CD28(-/-) mice failed to eradicate the parasites that persisted in the blood for >3 mo after infection. In addition, drug-cured CD28(-/-) mice were unable to generate memory T cells, develop an anamnesic IgG response, or eliminate the parasites from a secondary challenge. The incapacity of CD28(-/-) mice to acquire a full protective immunity to P. chabaudi correlated with an impaired production of specific IgG2a. Moreover, reinfected CD28(-/-) mice were protected by the adoptive transfer of serum from reinfected CD28(+/+) mice containing specific IgG2a. Our results demonstrate that the polyclonal lymphocyte response is only partially affected by the absence of CD28, but this coreceptor is essential to generate specific T and B cell responses required for complete protection against P. chabaudi malaria.
authors.affiliation: Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil. stellato@usp.br
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Elias
authors.forename: Luiz R
authors.initials: LR
authors.lastname: Sardinha
authors.forename: Karina R B
authors.initials: KR
authors.lastname: Bastos
authors.forename: Cláudia A
authors.initials: CA
authors.lastname: Zago
authors.forename: Ana Paula Freitas
authors.initials: AP
authors.lastname: da Silva
authors.forename: José M
authors.initials: JM
authors.lastname: Alvarez
authors.forename: Maria Regina D'Império
authors.initials: MR
authors.lastname: Lima
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D018106:CD28 Antigens / Q000235:genetics / Q000502:physiology*; D002999:Clone Cells; D018985:Epitopes, B-Lymphocyte / Q000235:genetics / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D005260:Female; D007117:Immunization, Secondary; D007156:Immunologic Memory / Q000235:genetics; D008288:Malaria / Q000097:blood* / Q000235:genetics / Q000276:immunology* / Q000469:parasitology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016788:Plasmodium chabaudi / Q000254:growth & development / Q000276:immunology*; D013163:Splenomegaly / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology
chemical_list: D018106:CD28 Antigens; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte