Jason Whitmire, PhD

Assistant Professor
Carolina Vaccine Institute and
Department of Genetics

Research Interests

Key words:  viral immunology, memory T cell differentiation, B cell differentiation, vaccines, inflammation, microbial immunology

Memory T cell differentiation and the role of inflammatory cytokines
The need for improved vaccine efficacy is underscored by the looming threat of an influenza pandemic, the recent outbreak of SARS, and the continued spread of HIV and HCV. CD4 (T-helper) cells are induced after these infections and after vaccinations. They play a central “command and control” role in coordinating and enhancing the immune response to a number of pathogens. T-helper cells are essential for long-lasting humoral immunity, and recent studies show that they enhance early cytotoxic T cell responses and sustain CD8+ T cell memory, underscoring their key role in immune protection. My research interests center on understanding how virus reactive CD4 T cell responses are generated and maintained over time. My long-range goals are to identify specific molecular pathways that can be manipulated to enhance vaccine-induced T cell memory.

Much of the research in my lab is focused on understanding how inflammatory cytokines and costimulatory molecules influence the formation of virus-specific memory T cells and B cells. Interferons (IFN) are produced early during infection, and they function to reduce the replication of intracellular pathogens. My investigations have revealed an additional function: type-1 (IFNab) and type-2 (IFNg) interferons signal directly into antiviral T cells to enhance the formation of antiviral memory T cells by 100-fold. I am currently examining the molecular and cellular mechanisms by which interferons propel T cell responses, and I am exploring methods to deliver these signals into T cells to increase memory.

I am also investigating the interplay between B cells and T cells. It is well established that CD4+ T cells deliver signals to B cells, which enables B cells to differentiate into memory B cells and plasma cells; this interaction is crucial for driving humoral immunity against many pathogens. I reported that B cells are also needed to form CD4+ T cell memory.  I am currently examining the hypothesis that B cells provide a survival signal that enables virus-specific CD4+ T cells to differentiate into memory cells.

Overall, the results from the research in my lab should lead to an improved understanding of how to design vaccines that stimulate long-standing protective immunity.

Publications

Selected publications

Whitmire, J.K., Asano, M.S., Kaech, S.M., Sarkar, S., Hannum, L.G., Shlomchik, M.J., Ahmed, R. Requirement of B cells for generating CD4+ T cell memory. J. Immunol. 182: 1868, 2009.

Whitmire, J.K., Eam, B., Whitton, J.L. Mice deficient in stem cell antigen-1 (Sca1, Ly-6A/E) develop normal primary and memory CD4+ and CD8+ T cell responses to virus infection. Eur. J. Immunol. 39, 2009.

Whitmire, J.K., Eam, B., Whitton, J.L. Tentative T cells: memory cells are quick to respond, but slow to divide. PloS Pathog. 4: e1000041, 2008.

Whitmire, J.K., Benning, N., Eam, B., Whitton, J.L. Increasing the CD4+ T cell precursor frequency leads to competition for IFNg, thereby degrading memory cell quantity and quality. J. Immunol. 180: 6777, 2008.

Whitmire, J.K., Eam, B., Benning, N., Whitton, J.L. Direct interferon-g signaling dramatically enhances CD4+ and CD8+ T cell memory. J. Immunol. 179: 1190, 2007.

Whitmire, J.K., Benning N., Whitton, J.L. Precursor frequency, nonlinear proliferation, and functional maturation of virus-specific CD4+ T cells. J. Immunol. 176: 3028, 2006.

Contact Information

Carolina Vaccine Institute and
The Department of Genetics
UNC-CH School of Medicine
9024 Burnett Womack, CB#7292
101 Manning Dr.
Chapel Hill, NC 27599-7292

Office: Rm. 9004, Burnett-Womack
Phone (office & lab): 919-966-4026
FAX: 919-843-6924

Email: jwhitmir@email.unc.edu