|Department Affiliations||Molecular Microbiology and Immunology|
|SOM Address||E3630 Bloomberg School of Public Health Building|
Tracy Allen 2010 – 2013
Our current research focuses on the characterization of the cellular and molecular mechanisms underlying the induction of protective T-cell mediated immunity against malaria parasites. We generated strains of transgenic mice bearing T cell receptors specific for parasite antigens recognized by CD8+ or CD4+ T cells. Using these mice, we are currently conducting studies to characterize the molecular and genetic events involved in the development and maintenance of effector anti-parasite T cells, and the mechanisms by which CD4+ /CD8+ T cells interact during the development of immunity against infection. Our research combines in vivo immuno-physiology studies together with molecular and genetic approaches. Particular emphasis is given to research aimed at characterizing the mechanisms involved in tissue-trafficking of activated CD8+ T cells and identifying the nature of the molecular processes leading to the development of memory subsets.
These studies using a rodent parasite system provides the rationale and experimental basis for research aimed at developing an anti-malaria vaccine for humans. Furthermore, these rodent models are excellent systems for studying the general principles of protective immunity against intracellular pathogens, as they develop in vivo. These studies enhance our understanding of the immune system at the most fundamental level.
- Chakravarty S., Cockburn I A.., Kuk S., Overstreet M., Sacci J., and Zavala F. 2007. CD8+ T lymphocytes protective against malaria liver stages are primed in skin-draining lymph nodes. Nature Med. (September, in press)
- Pinheiro A , Morrot, A., Chakravarty S., Overstreet, M., Bream,JH., Irusta, PM.,and Zavala F. 2007. IL-4 induces a wide-spectrum intracellular signaling cascade in CD8+ T cells J. Leuk. Biol 81-1102-10
- Kumar K A, Sano GI, Boscardin S, Nussenzweig RS, Nussenzweig MC, Zavala F and Nussenzweig V.2006 The circumsporozoite protein is an immunodominant protective antigen in irradiated sporozoites. Nature 444:937-40
- Morrot, A., Hafalla J.C., Cockburn I.A., Carvalho L.H., and Zavala F. 2005. IL-4 R expression is required for the development of protective memory responses against liver stages of malaria parasites. J Exp Med. 202 :551-60.
- Hafalla, JC., Sano. G, Carvalho L., Morrrot A., and Zavala F. 2002. Short-term antigen presentation and single clonal burst limit the magnitude of the CD8+ T cell responses against malaria liver stages. Proc. Natl. Acad. Sci.. (USA) 99:11819-11824
- Carvalho, L.H., Sano,G.,Hafalla J.C, Morrot A., Curotto M. and Zavala F. 2002. IL-4 secreting CD4+ T cells are crucial to the development of CD8+ T cell responses against malaria liver stages. Nature. Med. 8:166-170