Migratory properties of naive, effector, and memory CD8(+) T cells.
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 (CD8(IL-15)) resemble central memory cells in phenotype and function. In contrast, primed CD8(+) T cells cultured in IL-2 (CD8(IL-2)) become cytotoxic effector cells. Here, the migratory behavior of these two subsets was investigated. Naive, CD8(IL-15) cells and, to a lesser degree, CD8(IL-2) cells localized to T cell areas in the spleen, but only naive and CD8(IL-15) cells homed to lymph nodes (LNs) and Peyer's patches. Intravital microscopy of peripheral LNs revealed that CD8(IL-15) cells, but not CD8(IL-2) cells, rolled and arrested in high endothelial venules (HEVs). Migration of CD8(IL-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, CD8(IL-2) cells were 12 times more efficient in migrating to inflamed peritoneum than CD8(IL-15) cells. Furthermore, CD8(IL-15) cells proliferated rapidly upon reencounter with antigen at sites of inflammation. Thus, central memory-like CD8(IL-15) cells home avidly to lymphoid organs and moderately to sites of inflammation, where they mediate rapid recall responses, whereas CD8(IL-2) effector T cells accumulate in inflamed tissues, but are excluded from most lymphoid organs.
Weninger
W
W
The Center for Blood Research, Harvard Medical School, Boston, MA 02115, USA.
Crowley
M A
MA
Manjunath
N
N
von Andrian
U H
UH
D000818:Animals; D001775:Blood Circulation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002455:Cell Division; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D005260:Female; D007156:Immunologic Memory; D007249:Inflammation / Q000276:immunology; D019409:Interleukin-15 / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008208:Lymphatic System / Q000166:cytology / Q000276:immunology; D008297:Male; D051379:Mice; D010581:Peyer's Patches / Q000166:cytology / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D019409:Interleukin-15; D007376:Interleukin-2