CCR8 expression identifies CD4 memory T cells enriched for FOXP3+ regulatory and Th2 effector lymphocytes

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 leukocyt...

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Vydáno v:	The Journal of immunology (1950) Ročník 177; číslo 10; s. 6940
Hlavní autoři:	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
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States 15.11.2006
Témata:	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
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Shrnutí:	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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0022-1767
DOI:	10.4049/jimmunol.177.10.6940