CD4+ T cells can be segregated into distinct subsets based on their pattern of cytokine production. CD4+ T cells that secrete IFN-g are termed Th1 cells while cells that secrete IL-4, IL-5 and IL-13 are termed Th2 cells. While Th1 cells are essential in mediating protection against a variety of intracellular infections they also mediate pro-inflammatory responses associated with a variety of autoimmune diseases. Th2 cells have a role in counter-regulating Th1 responses and are associated with allergic and asthmatic disease. These studies examine the factors, which regulate how T helper responses are sustained in vivo. Recent work explores the mechanism by which CD4+/IFN-g effector cells die in vivo. The work studies the capacity of distinct lineages of Th1 cells to survive in vivo following antigenic stimulation. Populations of Th1 cells which differ in their ability to secrete IL-2 and IFN-g are studied. A major emphasis is to understand differences in how these populations of cells are regulated in vivo. The studies over the past year have shown the following:? ? ? 1. Th1 cells have a linear transition from effector cells secreting IFN-g and IL-2 to IFN-g only and then death.? 2. Th1 cells that have been repetitively stimulated confer better protection upon challenge with Listeria monocytogenes than cells that have undergone only one round of activation. However, repetitively stimulated cells are not long-lived.? 3. Intracellular proteins such as Foxo-3a and BIM are differentially expressed in distinct populations of Th1 cells. Expression of such proteins correlate with cell death and limited memory capacity of repetitively stimulated Th1 cells.
| Foulds, Kathryn E; Rotte, Masashi J; Paley, Michael A et al. (2008) IFN-gamma mediates the death of Th1 cells in a paracrine manner. J Immunol 180:842-9 |
| Seder, Robert A; Darrah, Patricia A; Roederer, Mario (2008) T-cell quality in memory and protection: implications for vaccine design. Nat Rev Immunol 8:247-58 |
| Darrah, Patricia A; Patel, Dipti T; De Luca, Paula M et al. (2007) Multifunctional TH1 cells define a correlate of vaccine-mediated protection against Leishmania major. Nat Med 13:843-50 |
| Foulds, Kathryn E; Rotte, Masashi J; Seder, Robert A (2006) IL-10 is required for optimal CD8 T cell memory following Listeria monocytogenes infection. J Immunol 177:2565-74 |
| Foulds, Kathryn E; Wu, Chang-you; Seder, Robert A (2006) Th1 memory: implications for vaccine development. Immunol Rev 211:58-66 |
| Pulendran, Bali; Seder, Robert A (2005) Host-pathogen interactions in the 21st century. Curr Opin Immunol 17:335-7 |
| Seder, Robert A; Sacks, David L (2004) Memory may not need reminding. Nat Med 10:1045-7 |
