CCR7 is required for the in vivo function of CD4+ CD25+ regulatory T cells.
CCR7-mediated migration of naive T cells into the secondary lymphoid organs is a prerequisite for their encounter with mature dendritic cells, the productive presentation of cognate antigen, and consequent T cell proliferation and effector differentiation. Therefore, CCR7 was suggested to play an important role in the initiation of adaptive immune responses. In this study, we show that primary immunity can also develop in the absence of CCR7. Moreover, CCR7-deficient knockout (KO) mice display augmented immune responses. Our data cumulatively suggest that enhanced immunity in CCR7 KO mice is caused by the defective lymph node (LN) positioning of FoxP3(+) CD4(+) CD25(+) regulatory T cells (T reg cells) and the consequent impediment of their function. The FoxP3(+) T reg cells express CCR7 and, after their adoptive transfer, migrate into the LNs of wild-type mice. Here, they proliferate in situ upon antigen stimulation and inhibit the generation of antigen-specific T cells. Conversely, transferred CCR7-deficient T reg cells fail to migrate into the LNs and suppress antigen-induced T cell responses. The transfer of combinations of naive and T reg cells from wild-type and CCR7 KO mice into syngeneic severe combined immunodeficient mice directly demonstrates that CCR7-deficient T reg cells are less effective than their wild-type counterparts in preventing the development of inflammatory bowel disease.
Schneider
Martin A
MA
Novartis Institutes for BioMedical Research, A1235 Vienna, Austria.
Meingassner
Josef G
JG
Lipp
Martin
M
Moore
Henrietta D
HD
Rot
Antal
A
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D049109:Cell Proliferation; D003877:Dermatitis, Contact / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051858:Forkhead Transcription Factors / Q000378:metabolism; D005786:Gene Expression Regulation; D018960:Hyaluronan Receptors / Q000378:metabolism; D039001:Integrin alpha Chains / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism*; D008198:Lymph Nodes / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D054390:Receptors, CCR2; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013154:Spleen / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*
D015703:Antigens, CD; C515335:Ccr2 protein, mouse; C515371:Ccr7 protein, mouse; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D018960:Hyaluronan Receptors; D039001:Integrin alpha Chains; D053645:Interleukin-2 Receptor alpha Subunit; D011948:Receptors, Antigen, T-Cell; D054390:Receptors, CCR2; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; C091367:alpha E integrins