An effective CD8+ T cell response is critical for protection from intracellular infectious agents and tumor cells. Unfortunately, the molecular mechanisms of CD8+ T cell effector and memory establishment are unclear, preventing the development of effective vaccines and immunotherapeutics directed against many infectious threats and cancers. As a post-doctoral fellow in Dr. Reiner's laboratory, I have helped to demonstrate that mice with T cells lacking the two highly homologous T-box transcription factors, Eomesodermin (Eomes) and T-bet, develop an inappropriate effector CD8+ T cell response to acute infection with lymphocytic choriomeningitis virus (LCMV), fail to clear the infection, and die from inappropriate CD8+ T cell interleukin-17 secretion. Further work from Dr. Reiner's laboratory and my preliminary data demonstrate preferential effector differentiation in CD8+ T cells lacking Eomes and memory differentiation in CD8+ T cells lacking T-bet in the context of LCMV infection. These data lead to the hypothesis that the differentiation of CD8+ T cells into effector and memory compartments during an immune response is determined by the relative expression of T-bet and Eomes. In the project proposed, I will test this model of CD8+ T cell differentiation in two different types of immune challenges and will also investigate the transcriptional targets by which Eomes promotes the development of CD8+ T cell memory. In the first aim, CD8+ T cell effector and memory differentiation will be assessed in mice lacking T-bet, Eomes, or both, after infection with listeria monocytogenes, a bacterial pathogen. In the second aim, I will assess effector and memory CD8+ T cell differentiation during an anti-cancer immune response in mice lacking T- bet, Eomes, or both. In the third aim, I will combine a candidate target approach with an unbiased approach to determine the transcriptional targets of Eomes that are important in memory CD8+ T cell differentiation. The proposed work will help define the transcriptional regulatory mechanisms that underlie T cell differentiation over the course of an immune response and may provide key insights into how to clinically manipulate T cells to maximize their therapeutic potential. Through these studies I will gain the expertise required to be an independent investigator in tumor immunology and cellular therapy.

Public Health Relevance

The project proposed incorporates three models of human disease: Viral infection (lymphocytic choriomeningitis virus, LCMV), bacterial infection (listeria monoctyogenes, LM), and cancer (lymphoma). Dr. Banerjee's project will aid in the development of T cell immunotherapeutic and vaccine strategies in the treatment and/or prevention of intracellular infections and cancer.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Clinical Investigator Award (CIA) (K08)
Project #
Application #
Study Section
Special Emphasis Panel (ZHL1-CSR-U (F1))
Program Officer
Welniak, Lisbeth A
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Maryland Baltimore
Internal Medicine/Medicine
Schools of Medicine
United States
Zip Code
Chornoguz, Olesya; Hagan, Robert S; Haile, Azeb et al. (2017) mTORC1 Promotes T-bet Phosphorylation To Regulate Th1 Differentiation. J Immunol 198:3939-3948
Furusawa, Aki; Sadashivaiah, Kavitha; Singh, Zeba N et al. (2016) Inefficient megakaryopoiesis in mouse hematopoietic stem-progenitor cells lacking T-bet. Exp Hematol 44:194-206.e17
Simpson, Haley M; Khan, Rashid Z; Song, Chang et al. (2015) Concurrent Mutations in ATM and Genes Associated with Common ? Chain Signaling in Peripheral T Cell Lymphoma. PLoS One 10:e0141906
Song, Chang; Sadashivaiah, Kavitha; Furusawa, Aki et al. (2014) Eomesodermin is required for antitumor immunity mediated by 4-1BB-agonist immunotherapy. Oncoimmunology 3:e27680
Matsuura, Hiroshi; Hartl, Dominik; Kang, Min-Jong et al. (2011) Role of breast regression protein-39 in the pathogenesis of cigarette smoke-induced inflammation and emphysema. Am J Respir Cell Mol Biol 44:777-86
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