Beyond Type 1 Regulatory T Cells: Co-expression of LAG3 and CD49b in IL-10-Producing T Cell Lineages.
Type 1 regulatory CD4+ T (Tr1) cells express high levels of the immunosuppressive cytokine IL-10 but not the master transcription factor Foxp3, and can suppress inflammation and promote immune tolerance. In order to identify and obtain viable Tr1 cells for research and clinical applications, co-expression of CD49b and LAG3 has been proposed as a unique surface signature for both human and mouse Tr1 cells. However, recent studies have revealed that this pattern of co-expression is dependent on the stimulating conditions and the differentiation stage of the CD4+ T cells. Here, using an IL-10GFP/Foxp3RFP dual reporter transgenic murine model, we demonstrate that co-expression of CD49b and LAG3 is not restricted to the Foxp3- Tr1 cells, but is also observed in Foxp3+ T regulatory (Treg) cells and CD8+ T cells that produce IL-10. Our data indicate that IL-10-producing Tr1 cells, Treg cells and CD8+ T cells are all capable of co-expressing LAG3 and CD49b in vitro following differentiation under IL-10-inducing conditions, and in vivo following pathogenic insult or infection in the pulmonary mucosa. Our findings urge caution in the use of LAG3/CD49b co-expression as sole markers to identify Tr1 cells, since it may mark IL-10-producing T cell lineages more broadly, including the Foxp3- Tr1 cells, Foxp3+ Treg cells, and CD8+ T cells.
['Huang|Weishan|W|', 'Solouki|Sabrina|S|', 'Carter|Chavez|C|', 'Zheng|Song-Guo|SG|', 'August|Avery|A|']
D000818:Animals D015703:Antigens, CD D015415:Biomarkers D018414:CD8-Positive T-Lymphocytes D002454:Cell Differentiation D019070:Cell Lineage D002478:Cells, Cultured D051858:Forkhead Transcription Factors D006801:Humans D007108:Immune Tolerance D039421:Integrin alpha2 D016753:Interleukin-10 D051379:Mice D008810:Mice, Inbred C57BL D018345:Mice, Knockout D008822:Mice, Transgenic D050378:T-Lymphocytes, Regulatory
T cell IL-10 Foxp3 farmer's lung disease house dust mite influenza infection lung inflammation parasitic infection