CCR7 Expression and Memory T Cell Diversity in Humans
Abstract
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 alpha(4)beta(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 CD…
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Lymph nodes and tonsils are enriched in central memory CD4+ T-cells, whereas lungs and gastrointestinal mucosa contain mainly effector memory CD4+ T-cells.
“The lymph nodes and tonsils are enriched in central memory CD4 + T-cells, whereas the lungs and gastrointestinal mucosa contain mainly effector memory CD4 + T-cells (Campbell et al., 2001;Picker, 2006).”
From Monoclonal antibody TGN1412 trial failure explained by species differences in CD28 expression on CD4 <sup>+</sup> effector memory T‐cells (2010) · cites this paper as Campbell et al., 2001
Central and effector memory T-cells have different tissue distribution patterns compared with peripheral blood.
“Conversely, central and effector memory T-cells show a different pattern of distribution within the tissues compared with peripheral blood (Campbell et al., 2001;Picker, 2006).”
From Monoclonal antibody TGN1412 trial failure explained by species differences in CD28 expression on CD4 <sup>+</sup> effector memory T‐cells (2010) · cites this paper as Campbell et al., 2001
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- Authors
- Campbell, J. J., Murphy, K. E., Kunkel, E. J., Brightling, C. E., Soler, D., Shen, Z., Boisvert, J., Greenberg, H. B., Vierra, M. A., Goodman, S. B., Genovese, M. C., Wardlaw, A. J., Butcher, E. C., & Wu, L.
- Affiliations
- Harvard University (US)
- Takeda Oncology (United States) (US)
- VA Palo Alto Health Care System (US)
- University of Leicester (GB)
- Stanford Medicine (US)
- ORCID
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2001-01
- Volume
- 166
- Issue
- 2
- Pages
- 877-884
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1678352491
- Cited by
- 335
- References
- 36
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 9 · 2023: 7 · 2022: 6 · 2021: 7 · 2020: 15 · 2019: 11 · 2018: 3 · 2017: 5 · 2016: 6 · 2015: 9 · 2014: 8 · 2013: 16 · 2012: 13
- FWCI
- 13.09
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ai037832-05)
- National Institute of General Medical Sciences (GM37732)
- National Institute of Allergy and Infectious Diseases (AI46784, AI 37832)
- Topics
- Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Keywords
- CCR7, memory T cells, T cell homing, high endothelial venules, secondary lymphoid organs, CD27, CXCR5, L-selectin, CCL17, CCL22, chemokine receptors, T cell activation, tonsil, cutaneous lymphocyte antigen, adhesion molecules, dendritic cells, tissue-resident lymphocytes
- MeSH terms
- Bronchi, Cells, Cultured, Chemotaxis, Leukocyte, Humans, Immunologic Memory, Intestinal Mucosa, Organ Specificity, Skin, Synovial Membrane, Palatine Tonsil, Biomarkers, CD4-Positive T-Lymphocytes, Immunophenotyping, T-Lymphocyte Subsets, CD8 Antigens, Tumor Necrosis Factor Receptor Superfamily, Member 7, CD8-Positive T-Lymphocytes, L-Selectin, Receptors, Chemokine, Receptors, CCR7
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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