CD4+CD25-LAG-3+ T cells in mouse and human.
We have recently reported a murine novel regulatory T cell population, CD4(+)CD25(-)LAG-3(+) regulatory T cells (Tregs). Microarray analysis revealed that CD4(+)CD25(-)LAG-3(+) Tregs had a unique mRNA expression profile that was different from the conventional CD4(+)CD25(+) regulatory T cells. In particular, CD4(+)CD25(-)LAG-3(+) Tregs characteristically expressed early growth response gene 2 (Egr-2) that was reported to be associated with the induction of anergy. CD4(+)CD25(-)LAG-3(+) Tregs produced high-amount of IL-10 in response to TCR stimulation and showed immunosuppressive activity in vitro and in vivo. Retroviral gene transfer of Eg-2 converted naïve CD4(+) T cells into IL-10-secreting and LAG-3-expressing T cells, and Egr-2 transduced CD4(+) T cells exhibited antigen-specific immunosuppressive capacity in vivo. On the basis of these observations, we have attempted to identify a human counterpart of murine CD4(+)CD25(-)LAG-3(+) Tregs in human. CD4(+)CD25(-)LAG-3(+) T cells were found in human in similar pattern as murine CD4(+)CD25(-)LAG-3(+) Tregs. In the quantitative PCR, human CD4(+)CD25(-)LAG-3(+) T cells expressed high levels of IL-10. From the microarray analysis, we found the close similarity between human CD4(+)CD25(-)LAG-3(+) T cells and murine CD4(+)CD25(-)LAG-3(+) Tregs. Therefore, human CD4(+)CD25(-)LAG-3(+) T cells might be a human counterpart of murine CD4(+)CD25(-)LAG-3(+) Tregs.
Sumitomo
Shuji
S
Department of Allergy and Rheumatology, Graduate School of Medicine, the University of Tokyo.
Yamamoto
Kazuhiko
K
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015551:Autoimmunity / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D051767:Early Growth Response Protein 2 / Q000235:genetics; D015870:Gene Expression; D018014:Gene Transfer Techniques; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D016753:Interleukin-10 / Q000378:metabolism; D051379:Mice; D046228:Microarray Analysis; D016133:Polymerase Chain Reaction; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D000093322:Lymphocyte Activation Gene 3 Protein
D015703:Antigens, CD; D051767:Early Growth Response Protein 2; C497327:Egr2 protein, mouse; D011948:Receptors, Antigen, T-Cell; D016753:Interleukin-10; D000093322:Lymphocyte Activation Gene 3 Protein