CD8+ T cells play a critical role in host defense against microbes pertinent to biodefense. A hallmark of adaptive immunity against agents such as Listeria monocytogenes, LCMV virus, and Toxoplasma gondii is heterogeneity of cell fate among antigen-experienced CD8+ T cells. Substantial preliminary evidence outlined in this proposal indicates that the first division of a CD8+ T cell responding to a pathogen, in vivo, is characterized by unequal partitioning of proteins with established roles in signaling, cell fate specification, and asymmetric cell division. In addition, the first daughter T cells of the immune response appear to be differentially fated as precursors of the effector and memory lineages. This project will test whether asymmetric cell division is a general feature of the CD8+ T cell response against pathogens, whether ancestral regulators of cell polarity are responsible for establishing cytoskeletal features necessary for asymmetric division, and how asymmetrically inherited signaling proteins could mediate fate disparity in daughter T cells. These studies should provide a framework for rational engineering of immune responses and vaccines against agents of biodefense, and address fundamental uncertainties regarding the principle of clonal selection of lymphocytes in response to infectious diseases.

Public Health Relevance

Specialized white blood cells, called lymphocytes, increase in number to help protect us against infections. This project will provide fundamental insight into how immunity against re-infection is maintained for one's entire life. This proposal is a response to a continuing initiative in Biodefense research sponsored by the NIAID.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
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Study Section
Cellular and Molecular Immunology - B Study Section (CMIB)
Program Officer
Lapham, Cheryl K
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Columbia University (N.Y.)
Schools of Medicine
New York
United States
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Paley, Michael A; Gordon, Scott M; Bikoff, Elizabeth K et al. (2013) Technical Advance: Fluorescent reporter reveals insights into eomesodermin biology in cytotoxic lymphocytes. J Leukoc Biol 93:307-15
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Qui, Harry Z; Hagymasi, Adam T; Bandyopadhyay, Suman et al. (2011) CD134 plus CD137 dual costimulation induces Eomesodermin in CD4 T cells to program cytotoxic Th1 differentiation. J Immunol 187:3555-64
Banerjee, Arnob; Gordon, Scott M; Intlekofer, Andrew M et al. (2010) Cutting edge: The transcription factor eomesodermin enables CD8+ T cells to compete for the memory cell niche. J Immunol 185:4988-92
Kinjyo, Ichiko; Gordon, Scott M; Intlekofer, Andrew M et al. (2010) Cutting edge: Lymphoproliferation caused by Fas deficiency is dependent on the transcription factor eomesodermin. J Immunol 185:7151-5

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