There is very good reason to be interested in this project. Lots of animal model work. This is just a random abstract, for a flavor.........
The Journal of Experimental Medicine, Volume 194, Number 7, October 1, 2001 953-966
Migratory Properties of Naive, Effector, and
Memory CD8+ T Cells
Wolfgang Weningera,b, Maura A. Crowleya, N. Manjunatha,c, and Ulrich H. von Andriana,b
a The Center for Blood Research, Harvard Medical School, Boston, MA 02115
b Department of Pathology, Harvard Medical School, Boston, MA 02115
c Department of Pediatrics, Harvard Medical School, Boston, MA 02115
Correspondence to: Ulrich H. von Andrian, The Center for Blood Research, 200 Longwood Ave., Boston, MA 02115. Tel:617- 278-3130
Fax:617-278-3190 E-mail:uva@cbr.med.harvard.edu.
It has been proposed that two different antigen-experienced T cell subsets may be distinguishable by their preferential ability to
home to lymphoid organs (central memory cells) or nonlymphoid tissues (effector memory/effector cells). We have shown
recently that murine antigen-primed CD8+ T cells cultured in interleukin (IL)-15 (CD8IL-15) resemble central memory cells in
phenotype and function. In contrast, primed CD8+ T cells cultured in IL-2 (CD8IL-2) become cytotoxic effector cells. Here, the
migratory behavior of these two subsets was investigated. Naive, CD8IL-15 cells and, to a lesser degree, CD8IL-2 cells localized
to T cell areas in the spleen, but only naive and CD8IL-15 cells homed to lymph nodes (LNs) and Peyer's patches. Intravital
microscopy of peripheral LNs revealed that CD8IL-15 cells, but not CD8IL-2 cells, rolled and arrested in high endothelial
venules (HEVs). Migration of CD8IL-15 cells to LNs depended on L-selectin and required chemokines that bind CC
chemokine receptor (CCR)7. Both antigen-experienced populations, but not naive T cells, responded to inflammatory
chemokines and accumulated at sites of inflammation. However, CD8IL-2 cells were 12 times more efficient in migrating to
inflamed peritoneum than CD8IL-15 cells. Furthermore, CD8IL-15 cells proliferated rapidly upon reencounter with antigen at sites
of inflammation. Thus, central memory-like CD8IL-15 cells home avidly to lymphoid organs and moderately to sites of
inflammation, where they mediate rapid recall responses, whereas CD8IL-2 effector T cells accumulate in inflamed tissues, but
are excluded from most lymphoid organs. |
