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 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.
Soler
Dulce
D
Inflammation, Millennium Pharmaceuticals, Cambridge, MA 02139, USA. dsoler@mpi.com
Chapman
Tobias R
TR
Poisson
Louis R
LR
Wang
Lin
L
Cote-Sierra
Javier
J
Ryan
Mark
M
McDonald
Alice
A
Badola
Sunita
S
Fedyk
Eric
E
Coyle
Anthony J
AJ
Hodge
Martin R
MR
Kolbeck
Roland
R
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D054402:Chemokine CCL1; D019742:Chemokines, CC / Q000502:physiology; D002634:Chemotaxis, Leukocyte / Q000235:genetics / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000096:biosynthesis*; D006801:Humans; D007156:Immunologic Memory / Q000235:genetics; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D008252:Macaca fascicularis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054401:Receptors, CCR8; D019707:Receptors, Chemokine / Q000096:biosynthesis* / Q000097:blood / Q000172:deficiency / Q000502:physiology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
C065971:CCL1 protein, human; C103330:CCR8 protein, human; C502258:Ccl1 protein, mouse; C489319:Ccr8 protein, mouse; D054402:Chemokine CCL1; D019742:Chemokines, CC; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D054401:Receptors, CCR8; D019707:Receptors, Chemokine