CD4+ T Cells Acting Independently of Antibody Contribute to Protective Immunity to Plasmodium chabaudi Infection After Apical Membrane Antigen 1 Immunization
| Autor: | Anthony N. Hodder, Robin F. Anders, P E Crewther, Huara Yan, Michael F. Good, Huji Xu |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
CD4-Positive T-Lymphocytes
Molecular Sequence Data Immunology Protozoan Proteins Antibodies Protozoan Epitopes T-Lymphocyte Mice Nude Antigens Protozoan chemical and pharmacologic phenomena Parasitemia Lymphocyte Depletion Epitope Plasmodium chabaudi Mice Antigen Antibody Specificity Immunity Lymphopenia Malaria Vaccines parasitic diseases medicine Animals Immunology and Allergy Amino Acid Sequence Apical membrane antigen 1 B cell Mice Knockout B-Lymphocytes Mice Inbred BALB C Vaccines Synthetic biology Immune Sera fungi Membrane Proteins Receptors Antigen T-Cell gamma-delta Apical membrane biology.organism_classification Virology Immunity Innate Malaria Mice Inbred C57BL medicine.anatomical_structure biology.protein Female Antibody Injections Intraperitoneal |
| Zdroj: | The Journal of Immunology. 165:389-396 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.165.1.389 |
| Popis: | Apical membrane Ag 1 (AMA1) is a leading malaria vaccine candidate. Homologues of AMA1 can induce protection in mice and monkeys, but the mechanism of immunity is not understood. Mice immunized with a refolded, recombinant, Plasmodium chabaudi AMA1 fragment (AMA1B) can withstand subsequent challenge with P. chabaudi adami. Here we show that CD4+ T cell depletion, but not γδ T cell depletion, can cause a significant drop in antiparasite immunity in either immunized normal or immunized B cell KO mice. In normal mice, this loss of immunity is not accompanied by a decline in Ab levels. These observations indicate a role for AMA1-specific Ab-independent T cell-mediated immunity. However, the loss of immunity in normal CD4+ T cell-depleted mice is temporary. Furthermore, immunized B cell KO mice cannot survive infection, demonstrating the absolute importance of B cells, and presumably Ab, in AMA1-induced immunity. CD4+ T cells specific for a cryptic conserved epitope on AMA1 can adoptively transfer protection to athymic (nu/nu) mice, the level of which is enhanced by cotransfer of rabbit anti-AMA1-specific antisera. Recipients of rabbit antisera alone do not survive. Some protected recipients of T cells plus antisera do not develop their own AMA 1-specific Ab response, suggesting that AMA 1-specific CMI alone can protect mice. These data are the first to demonstrate the specificity of any protective CMI response in malaria and have important implications for developing a malaria vaccine. |
| Databáze: | OpenAIRE |
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