Gradual decline in malaria-specific memory T cell responses leads to failure to maintain long-term protective immunity to Plasmodium chabaudi AS despite persistence of B cell memory and circulating antibody.
The mechanisms responsible for the generation and maintenance of immunological memory to Plasmodium are poorly understood and the reasons why protective immunity in humans is so difficult to achieve and rapidly lost remain a matter for debate. A possible explanation for the difficulty in building up an efficient immune response against this parasite is the massive T cell apoptosis resulting from exposure to high-dose parasite Ag. To determine the immunological mechanisms required for long-term protection against P. chabaudi malaria and the consequences of high and low acute phase parasite loads for acquisition of protective immunity, we performed a detailed analysis of T and B cell compartments over a period of 200 days following untreated and drug-treated infections in female C57BL/6 mice. By comparing several immunological parameters with the capacity to control a secondary parasite challenge, we concluded that loss of full protective immunity is not determined by acute phase parasite load nor by serum levels of specific IgG2a and IgG1 Abs, but appears to be a consequence of the progressive decline in memory T cell response to parasites, which occurs similarly in untreated and drug-treated mice with time after infection. Furthermore, by analyzing adoptive transfer experiments, we confirmed the major role of CD4(+) T cells for guaranteeing long-term full protection against P. chabaudi malaria.
Freitas do Rosário
Ana Paula
AP
Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil. anapaulafreitas@yahoo.com
Muxel
Sandra Márcia
SM
Rodríguez-Málaga
Sérgio Marcelo
SM
Sardinha
Luiz Roberto
LR
Zago
Cláudia Augusta
CA
Castillo-Méndez
Sheyla Inés
SI
Alvarez
José Maria
JM
D'Império Lima
Maria Regina
MR
D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis / Q000097:blood*; D016175:B-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology* / Q000469:parasitology; D004912:Erythrocytes / Q000276:immunology / Q000469:parasitology; D005260:Female; D007113:Immunity, Innate / Q000187:drug effects / Q000235:genetics; D007156:Immunologic Memory / Q000187:drug effects / Q000235:genetics; D008288:Malaria / Q000188:drug therapy / Q000276:immunology* / Q000469:parasitology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018512:Parasitemia / Q000188:drug therapy / Q000276:immunology / Q000469:parasitology; D016788:Plasmodium chabaudi / Q000187:drug effects / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology* / Q000469:parasitology; D013997:Time Factors
D000913:Antibodies, Protozoan