Site-specific accumulation of recently activated CD4+ Foxp3+ regulatory T cells following adoptive transfer.
CD4(+) Foxp3(+)  regulatory T (Treg) cells are required for the maintenance of self-tolerance, as demonstrated by profound autoimmunity in mice and humans with inactivating Foxp3 mutations. Recent studies demonstrate that Treg cells are anatomically compartmentalized within secondary lymphoid organs based on their TCR repertoire and specific organ-protective function; however, whether this reflects differential homing or in situ selection is not known. Here, using Foxp3-GFP reporter mice, we have examined the ability of polyclonal Treg cells from cervical LNs to return to their site-of-origin following adoptive transfer to nonlymphopenic congenic recipients. We find that bulk cervical LN Treg cells do not home directly to cervical LNs but rather accumulate site specifically over time following transfer. Site-specific enrichment is both more rapid and more pronounced among a population of recently activated (CD69(+) ) Treg cells. These data suggest that compartmentalization of Treg cells within secondary lymphoid organs may be governed by antigen recognition and implicate CD69 as a potential marker of recently activated Treg cells recognizing locally expressed antigens.
Division of Rheumatology, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA. liebermans@email.chop.edu
Scott M
SM
Lieberman
Jiyeon S
JS
Kim
Evann
E
Corbo-Rodgers
Taku
T
Kambayashi
Jonathan S
JS
Maltzman
Edward M
EM
Behrens
Laurence A
LA
Turka
D019264:Adoptive Transfer; D000818:Animals; D015703:Antigens, CD / Q000502:physiology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology; D002451:Cell Compartmentation; D002465:Cell Movement; D051858:Forkhead Transcription Factors / Q000032:analysis*; D037181:Lectins, C-Type / Q000502:physiology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000502:physiology*; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D051858:Forkhead Transcription Factors; D037181:Lectins, C-Type; D000099192:CD69 Antigens; C498833:Foxp3 protein, mouse