CD4(+) T cells acting independently of antibody contribute to protective immunity to Plasmodium chabaudi infection after apical membrane antigen 1 immunization
- Author(s)
- Xu, HJ; Hodder, AN; Yan, HR; Crewther, PE; Anders, RF; Good, MF;
- Details
- Publication Year 2000-07-01,Volume 165,Issue #1,Page 389-396
- Journal Title
- JOURNAL OF IMMUNOLOGY
- Publication Type
- Journal Article
- Abstract
- 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. rc;lice 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 gamma delta 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.
- Publisher
- AMER ASSOC IMMUNOLOGISTS
- Keywords
- MEROZOITE SURFACE PROTEIN-1; CARBOXYL-TERMINAL FRAGMENT; BALB/C MICE; MALARIA; VACCINE; PARASITEMIA; FALCIPARUM; RESPONSES; EPITOPES; MSP1(19)
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2000-07-01 12:00:00