Differential expression of CCR7 defines two distinct subsets of human memory CD4+CD25+ Tregs.
Natural Tregs play an essential role in controlling self-tolerance but the in vivo sites of Treg-mediated suppression remain controversial. We have previously reported the identification of distinct naïve and memory Treg populations in human circulating lymphocytes. Here we show that memory Tregs contain high proportions of inflammatory chemokine-expressing cells and comprise two populations that differ in the expression of the lymphoid chemokine receptor CCR7 and represent the counterparts of conventional CCR7(+) central memory (CM) and CCR7(-) effector memory (EM) T cells. CM and EM Tregs exert comparable ex vivo suppressor functions but the EM population is more prominent among Tregs as compared to conventional CD4(+) T cells, and is the main Treg subset found in ovarian tumors. Our data suggest that a division of labor between CM and EM Tregs ensures tolerance at lymphoid and peripheral locations including tumor sites.
Tosello
Valeria
V
Ludwig Institute Clinical Trial Center, Division of Medical Oncology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Odunsi
Kunle
K
Souleimanian
Naira E
NE
Lele
Shashikant
S
Shrikant
Protul
P
Old
Lloyd J
LJ
Valmori
Danila
D
Ayyoub
Maha
M
D015704:CD4 Antigens / Q000378:metabolism*; D002478:Cells, Cultured; D016207:Cytokines; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D007376:Interleukin-2 / Q000494:pharmacology; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism*; D019041:L-Selectin / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000378:metabolism; D054400:Receptors, CCR7 / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism
C515370:CCR7 protein, human; D015704:CD4 Antigens; D016207:Cytokines; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D054400:Receptors, CCR7; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D019041:L-Selectin