IL-2 receptor signaling is essential for the development of Klrg1+ terminally differentiated T regulatory cells.
Thymic-derived natural T regulatory cells (Tregs) are characterized by functional and phenotypic heterogeneity. Recently, a small fraction of peripheral Tregs has been shown to express Klrg1, but it remains unclear as to what extent Klrg1 defines a unique Treg subset. In this study, we show that Klrg1(+) Tregs represent a terminally differentiated Treg subset derived from Klrg1(-) Tregs. This subset is a recent Ag-responsive and highly activated short-lived Treg population that expresses enhanced levels of Treg suppressive molecules and that preferentially resides within mucosal tissues. The development of Klrg1(+) Tregs also requires extensive IL-2R signaling. This activity represents a distinct function for IL-2, independent from its contribution to Treg homeostasis and competitive fitness. These and other properties are analogous to terminally differentiated short-lived CD8(+) T effector cells. Our findings suggest that an important pathway driving Ag-activated conventional T lymphocytes also operates for Tregs.
Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, FL 33101, USA.
Guoyan
G
Cheng
Xiaomei
X
Yuan
Matthew S
MS
Tsai
Eckhard R
ER
Podack
Aixin
A
Yu
Thomas R
TR
Malek
D019264:Adoptive Transfer; D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D046228:Microarray Analysis; D011971:Receptors, Immunologic / Q000276:immunology* / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
C451496:Klrg1 protein, mouse; D037181:Lectins, C-Type; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2