The subpopulation of CD4+CD25+ splenocytes that delays adoptive transfer of diabetes expresses L-selectin and high levels of CCR7.
Recently, CD4(+)CD25(+) T cells have been implicated in the control of diabetes, suggesting that the inflamed islets of Langerhans in prediabetic NOD mice are under peripheral immune surveillance. Here we show that CD4(+)CD25(+) splenocytes inhibit diabetes in cotransfer with islet-infiltrating cells. Furthermore, CD62L expression is necessary for this disease-delaying effect of CD4(+)CD25(+) cells in vivo, but not for their suppressor function in vitro. We demonstrate that the CD4(+)CD25(+)CD62L(+) splenocytes express CCR7 at high levels and migrate toward secondary lymphoid tissue chemokine and ELC (macrophage-inflammatory protein-3beta), lymphoid chemokines, whereas CD4(+)CD25(+)CD62L(-) splenocytes preferentially express CCR2, CCR4, and CXCR3 and migrate toward the corresponding inflammatory chemokines. These data demonstrate that CD4(+)CD25(+)CD62L(+), but not CD4(+)CD25(+)CD62L(-), splenocytes delay diabetes transfer, and that CD4(+)CD25(+) suppressor T cells are comprised of at least two subpopulations that behave differently in cotransfer in vivo and express distinct chemokine receptor and chemotactic response profiles despite demonstrating equivalent suppressor functions in vitro.
Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, CA 94305, USA.
Veronika
V
Szanya
Joerg
J
Ermann
Cariel
C
Taylor
Claire
C
Holness
C Garrison
CG
Fathman
D019264:Adoptive Transfer / Q000379:methods; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D015704:CD4 Antigens / Q000096:biosynthesis*; D002465:Cell Movement / Q000276:immunology; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D019742:Chemokines, CC / Q000502:physiology; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D016867:Immunocompromised Host / Q000276:immunology; D007515:Islets of Langerhans / Q000276:immunology / Q000473:pathology; D019041:L-Selectin / Q000096:biosynthesis*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000096:biosynthesis*; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis*; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000637:transplantation*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000637:transplantation*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism / Q000637:transplantation
D015415:Biomarkers; D015704:CD4 Antigens; C515461:Ccl19 protein, mouse; C515479:Ccl21c protein, mouse; C515371:Ccr7 protein, mouse; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D019742:Chemokines, CC; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D015375:Receptors, Interleukin-2; D019041:L-Selectin