Declínio gradual na resposta das células T específicas à malária leva à falha em manter a imunidade protetora de longa duração contra o Plasmodium chabaudi AS apesar da persistência das células B de memória e anticorpos circulantes

• Processo: 09/02171-1
• Modalidade de apoio: Auxílio à Pesquisa - Publicações científicas - Artigo
• Data de Início da vigência: 01 de abril de 2009
• Data de Término da vigência: 30 de setembro de 2009
• Área do conhecimento: Ciências Biológicas - Imunologia - Imunologia Celular
• Pesquisador responsável: Maria Regina D'Império Lima
• Beneficiário: Maria Regina D'Império Lima
• Instituição Sede: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brasil
• Assunto(s): Anticorpos Malária Memória imunológica Plasmodium chabaudi Linfócitos T Publicações de divulgação científica Artigo científico
• Palavra(s)-Chave do Pesquisador: Anticorpos | Células T | malária | memória imunológica | Imunologia da Parasitoses

Resumo

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 antigen. 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 antibodies, 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. (AU)