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
| Autor: | Sandra Marcia Muxel, Sérgio Marcelo Rodriguez-Málaga, Sheyla Inés Castillo-Méndez, Maria Regina D'Império Lima, José M. Alvarez, Cláudia Augusta Zago, Ana Paula Freitas do Rosário, Luiz Roberto Sardinha |
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| Rok vydání: | 2008 |
| Předmět: |
Adoptive cell transfer
Erythrocytes Time Factors Immunology B-Lymphocyte Subsets Antibodies Protozoan Parasitemia Parasite load Plasmodium chabaudi Mice Immune system T-Lymphocyte Subsets Immunity medicine Animals Immunology and Allergy B cell Mice Knockout biology biology.organism_classification medicine.disease Virology Immunity Innate Malaria Mice Inbred C57BL medicine.anatomical_structure Female Immunologic Memory Memory T cell |
| Zdroj: | The Journal of Immunology. 181:8344-8355 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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