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Joint Program in Transfusion Medicine, Children’s Hospital, and Harvard Medical School, Department of Pathology, Boston, MA 02115;
Laboratory of Immunology and Vascular Biology, Department of Pathology, and the Digestive Disease Center, Department of Medicine, Stanford University Medical School, Stanford, CA 94305;
Center for Molecular Biology and Medicine, Veterans Affairs, Palo Alto Health Care System, Palo Alto, CA 94304;
Millennium Pharmaceuticals, Inc., Cambridge, MA 02142;
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Division of Respiratory Medicine, Institute for Lung Health, Leicester University Medical School, Leicester, United Kingdom; and Departments of
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Microbiology and Immunology,
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Surgery,
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Functional Restoration, and
Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA 94305
CCR7, along with L-selectin and LFA-1, mediates homing of T cells
to secondary lymphoid organs via high endothelial venules (HEV). CCR7
has also been implicated in microenvironmental positioning of
lymphocytes within secondary lymphoid organs and in return of
lymphocytes and dendritic cells to the lymph after passage through
nonlymphoid tissues. We have generated mAbs to human CCR7, whose
specificities correlate with functional migration of lymphocyte subsets
to known CCR7 ligands. We find that CCR7 is expressed on the vast
majority of peripheral blood T cells, including most cells that express
adhesion molecules (cutaneous lymphocyte Ag
4
7 integrin) required 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) population,
as well as L-selectin(neg) cells, suggesting that these cells are
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 reciprocal expression of these two
receptors may contribute to differential positioning of resting vs
activated cells within the organ. Lymphocytes isolated 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
CD27(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 tissue.
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