CCR8 Expression Identifies CD4 Memory T Cells Enriched for FOXP3+ Regulatory and Th2 Effector Lymphocytes

• Published in: The Journal of immunology (1950) 2006-11, Vol.177 (10), p.6940-6951
• Main Authors: Soler, Dulce, Chapman, Tobias R, Poisson, Louis R, Wang, Lin, Cote-Sierra, Javier, Ryan, Mark, McDonald, Alice, Badola, Sunita, Fedyk, Eric, Coyle, Anthony J, Hodge, Martin R, Kolbeck, Roland
• Format: Article
• Language: English
• Subjects: Animals; CD4-Positive T-Lymphocytes - cytology; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; Chemokine CCL1; Chemokines, CC - physiology; Chemotaxis, Leukocyte - genetics; Chemotaxis, Leukocyte - immunology; Forkhead Transcription Factors - biosynthesis; Humans; Immunologic Memory - genetics; Immunophenotyping; Lymphocyte Activation - genetics; Lymphocyte Activation - immunology; Macaca fascicularis; Mice; Mice, Inbred C57BL; Mice, Knockout; Receptors, CCR8; Receptors, Chemokine - biosynthesis; Receptors, Chemokine - blood; Receptors, Chemokine - deficiency; Receptors, Chemokine - physiology; T-Lymphocytes, Regulatory - cytology; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism; Th2 Cells - cytology; Th2 Cells - immunology; Th2 Cells - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.177.10.6940

CD4+ Th2 cells are important regulators of allergic inflammation. CCR8 is thought to play a role in Th2-mediated responses, however, expression of CCR8 in peripheral blood has not been fully characterized. Using a fluorescent form of the ligand selective for CCR8 (F-CCL1), we identified the leukocytes expressing CCR8 in human, monkey, and mouse peripheral blood. CCR8 expression is primarily restricted to a subset of human CD4 memory T lymphocytes (15%). Approximately 40% of CCR8+CD4+ T cells express Th2 cytokines IL-4 or IL-13 while 13% express the Th1 cytokine IFN-gamma. In fact, 50% of all Th2, but only 5% of Th1, cells express CCR8. Upon anti-CD3/anti-CD28 mAb-mediated activation, CCR8+CD4+ T cells secrete 3- to 7-fold higher levels of IL-4, IL-5, IL-9, and IL-13 and 10- to 20-fold lower levels of IFN-gamma or IL-17, compared with CCR8-CD4+ memory T cells. Two-thirds of CCR8+CD4 T cells express cutaneous lymphocyte-associated Ag while the majority lack gut-homing receptors. CCR8+CD4+ cells express CCR7 and CD62L and are present in spleen and lymph nodes of mice. Approximately 25% of CCR8+CD4 T cells express CD25high while 20% of CCR8+CD4+ express the T regulatory cell transcription factor FOXP3 accounting for 60% of all FOXP3-expressing CD4+ T cells. In conclusion, CCR8 marks a diverse subset of CD4 memory T cells enriched for T regulatory and Th2 cells which have the potential for recruitment into sites of allergic inflammation where they could participate in the induction and regulation of the allergic response.