Resistance to acute Plasmodium chabaudi adami malaria in mice is mediated by non-antibody mechanisms of immunity. Adoptive cell transfer studies demonstrate that T cells are required for both the induction and expression of this form of immunity. The purpose of the proposed study is to determine which Lyt subsets of splenic T cells are involved. Lyt subsets of spleen cells from euthymic mice prepared by selective killing with anti-Lyt monoclonal antibody in the presence of complement or by panning rat anti-mouse Lyt coated spleen cells on petri plates coated with anti-rat Ig will be injected into histocopatible athymic nude mice prior to challenge with P. chadaudi adami. The resulting parasitemias will be plotted against time in order to see which Lyt subset(s) suppress infection. Also, Lyt subsets of spleen cells prepared from the spleens of P. chabaudi adami immune B-cell deficient mice as well as immunologically intact mice will be tested for their ability to adoptively transfer immunity to P chabaudi adami infection to irradiated homologous recipients. In order to define mechanisms of nonantibody immunity to P. chabaudi adami T-cell clones and T-cell hybrids constructed with spleen cells of immune mice will be tested for their capacity to protect nude mice against challenge infection. Similarly, soluble factors from protective cell lines will be characterized and tested for their ability to mediate protection in nude mice. Two additional parameters will be investigated in order to determine whether they can be correlated with protection achieved with Lyt fraction T-cell clones and T-cell hybrids. These are splenic macrophage activation as determined by chemiluminescence and the activation of splenic reticular cells. Finally, P. chabaudi adami antigens will be fractionated and characterized in terms of their ability to activate protecting cell populations as well as to induce protection in mice by immunization. This approach, which will attempt to correlate protection with cell function, factor-production, and effector cell activation, may provide a coherent physiologic picture of events which must transpire for the expression of antibody-independent immunity.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
Project #
Application #
Study Section
Tropical Medicine and Parasitology Study Section (TMP)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Hahnemann University
Schools of Medicine
United States
Zip Code
Weidanz, W P; Lafleur, G; Kita-Yarbro, A et al. (2011) Signalling through the IL-2 receptor ?(c) peptide (CD132) is essential for the expression of immunity to Plasmodium chabaudi adami blood-stage malaria. Parasite Immunol 33:512-6
Weidanz, William P; LaFleur, GayeLyn; Brown, Andrew et al. (2010) Gammadelta T cells but not NK cells are essential for cell-mediated immunity against Plasmodium chabaudi malaria. Infect Immun 78:4331-40
Lynch, Michelle M; Cernetich-Ott, Amy; Weidanz, William P et al. (2009) Prediction of merozoite surface protein 1 and apical membrane antigen 1 vaccine efficacies against Plasmodium chabaudi malaria based on prechallenge antibody responses. Clin Vaccine Immunol 16:293-302
van der Heyde, Henri C; Burns, James M; Weidanz, William P et al. (2007) Analysis of antigen-specific antibodies and their isotypes in experimental malaria. Cytometry A 71:242-50
van der Heyde, Henri C; Batchelder, Joan M; Sandor, Matyas et al. (2006) Splenic gammadelta T cells regulated by CD4+ T cells are required to control chronic Plasmodium chabaudi malaria in the B-cell-deficient mouse. Infect Immun 74:2717-25
Weidanz, William P; Batchelder, Joan M; Flaherty, P et al. (2005) Plasmodium chabaudi adami: use of the B-cell-deficient mouse to define possible mechanisms modulating parasitemia of chronic malaria. Exp Parasitol 111:97-104
Rummel, Thomas; Batchelder, Joan; Flaherty, Patrick et al. (2004) CD28 costimulation is required for the expression of T-cell-dependent cell-mediated immunity against blood-stage Plasmodium chabaudi malaria parasites. Infect Immun 72:5768-74
Gillman, Brad M; Batchelder, Joan; Flaherty, Patrick et al. (2004) Suppression of Plasmodium chabaudi parasitemia is independent of the action of reactive oxygen intermediates and/or nitric oxide. Infect Immun 72:6359-66
Cigel, Francine; Batchelder, Joan; Burns Jr, James M et al. (2003) Immunity to blood-stage murine malarial parasites is MHC class II dependent. Immunol Lett 89:243-9
Batchelder, Joan M; Burns Jr, James M; Cigel, Francine K et al. (2003) Plasmodium chabaudi adami: interferon-gamma but not IL-2 is essential for the expression of cell-mediated immunity against blood-stage parasites in mice. Exp Parasitol 105:159-66

Showing the most recent 10 out of 36 publications