CCR7 expression and memory T cell diversity in humans

CCR7, along with L-selectin and LFA-1, mediates homing of T cells to second ary lymphoid organs via high endothelial venules (HEV), CCR7 has also been implicated in microenvironmental positioning of lymphocytes within secondar y lymphoid organs and in return of lymphocytes and dendritic cells to the l ymph after passage through nonlymphoid tissues. We have generated mAbs to h uman CCR7, whose specificities correlate with functional migration of lymph ocyte subsets to known CCR7 ligands, We find that CCR7 is expressed on the vast majority of peripheral blood T cells, including most cells that expres s adhesion molecules (cutaneous lymphocyte Ag alpha (4)beta (7) integrin) r equired for homing to nonlymphoid tissues. A subset of CD27(neg) memory CD4 T cells from human peripheral blood is greatly enriched in the CCR7(neg) p opulation, as well as L-selectin(neg) cells, suggesting that these cells ar e incapable of homing to secondary lymphoid organs. Accordingly, CD27(neg) T cells are rare within tonsil, a representative secondary lymphoid organ. All resting T cells within secondary lymphoid organs express high levels of CCR7, but many activated cells lack CCR7, CCR7 loss in activated CD4 cells accompanies CXC chemokine receptor (CXCR)5 gain, suggesting that the recip rocal expression of these two receptors may contribute to differential posi tioning of resting vs activated cells within the organ. Lymphocytes isolate d from nonlymphoid tissues (such as skin, lung, or intestine) contain many CD27(neg) cells lacking CCR7, The ratio of CD27(neg)/CCR7(neg) cells to CD2 7(pos)/CCR7(pos) cells varies from tissue to tissue, and may correlate with the number of cells actively engaged in Ag recognition within a given tiss ue.