Faculty
| VLADIMIR P. BADOVINAC, Ph.D. Assistant Professor 137 Medical Research Center Iowa City, IA 52242-1182 B.S., University of Belgrade, Belgrade, Serbia, 1994 M.Sc., University of Belgrade, Belgrade, Serbia, 1997 Ph.D., University of Belgrade, Belgrade, Serbia, 1999 Postdoctoral Associate, University of Iowa, Department of Microbiology, 1999-2002 Research Scientist, University of Iowa, Department of Microbiology, 2002-2007 |
CD8 T cell responses
CD8 T cells recognize and respond to pathogen-encoded peptides displayed by MHC class I molecules on infected cells or on antigen (Ag)-presenting cells (APC) that have acquired these peptides through cross-presentation pathways. Activated CD8 T cells manifest an array of antimicrobial effector pathways and molecules, which eliminate infected cells (cytolysis) or recruit and activate other immune cells (cytokines). CD8 T cells are important in defense against viruses, intracellular bacteria and protozoan pathogens and are also potentially important in defense against malignancy. Thus, stimulation of pathogen-specific CD8 T cell responses is an important goal of vaccination.
Technologies such as MHC class I tetramer reagents, peptide-stimulated intracellular cytokine analysis and ELISPOT as well as the generation of pathogen-specific T cell receptor transgenic (TCR-tg) mice provide high resolution tools for analysis of the CD8 T cell response to infection or vaccination. The CD8 T cell response can be divided into four relatively distinct phases (Figure 1).
1) Initial activation, which is critically dependant on relatively stable (hours) interactions between naive T cells and mature, Ag- and costimulatory molecule-expressing dendritic cells (DC); 2) Proliferative expansion lasting 5-8 days where the pathogen-specific CD8 T cell numbers may increase by >10,000-fold. Clonal expansion is also associated with differentiation to effector T cells that migrate throughout the body to defend against infection; 3) Contraction in number by apoptosis where 90-95% of effector cells are eliminated over the ensuing week; and 4) Initiation and maintenance of the memory CD8 T cell pool by the cells surviving contraction. Recent studies collectively indicate that the expansion, contraction and memory phases of the CD8 T cell response are largely, if not completely independent of continued Ag-display, suggesting that a relatively brief encounter with Ag is sufficient to instigate the full program of CD8 T cell differentiation to memory. However, it has recently become clear that, in addition to Ag, a variety of signals must be integrated by the responding T cells to generate optimal responses and to ensure proper regulation of T cell homeostasis.
Our main goals are:
-To establish relevant experimental models to study antigen-experienced CD8 T cells in vivo;
- To determine the factors that influence generation, maintenance and function of memory CD8 T cells;
- To characterize CD8 T cells responding to multiple rounds of antigenic stimulations;
- To define homeostasis of tumor (self)-specific CD8 T cells;
Selected Publications:
1. Badovinac VP, Haring JS, and JT Harty. Initial TCR-transgenic precursor frequency dictates critical aspects of the CD8 T cell response to infection. Immunity 26, 827-841. (2007)
2. Badovinac VP, and JT Harty. Manipulating the rate of memory CD8 T cell generation after acute infection. The Journal of Immunology 179, 53-63. (2007)
3. Badovinac VP, and JT Harty. Programming, Demarcating and Manipulating CD8 T cell memory. Immunological Reviews 211, 67-80. (2006)
4. Haring JS*, Badovinac VP*, and JT Harty. Inflamming the CD8 T cell response. Immunity 25, 19-25. (2006)
5. Badovinac VP*, KAN Messingham*, A Jabbari, JS Haring, and JT Harty. Accelerated CD8+ T cell-memory and prime-boost response after dendritic-cell vaccination. Nature Medicine 11, 748-756. (2005)
6. Badovinac VP, BP Porter, and JT Harty. CD8+ T cell contraction is controlled by early inflamation. Nature Immunology 5, 809-817. (2004)
7. Badovinac VP, SE Hamilton, and JT Harty. Viral infection results in massive CD8+ T cell expansion and mortality in vaccinated perforin-deficient mice. Immunity 18, 463- 474. (2003)
8. Badovinac VP, BB Porter, and JT Harty.Programmed contraction of CD8+ T cells after infection. Nature Immunology 3, 619-626. (2002)
9. Badovinac VP, AR Tvinnereim, and JT Harty. Regulation of antigen-specific CD8+ T cell homeostasis by perforin and IFN-γ. Science 290, 1354-1357. (2000)
(See complete publications list at PubMed)