TY - JOUR
T1 - Beyond type 1 regulatory t cells
T2 - Co-expression of LAG3 and CD49b in IL-10-producing t cell lineages
AU - Huang, Weishan
AU - Solouki, Sabrina
AU - Carter, Chavez
AU - Zheng, Song Guo
AU - August, Avery
N1 - Funding Information:
We thank A. Redko for animal care and L. Zhang for technical assistance; Dr. E. Tait Wojno for N. brasiliensis; and Drs. D. Topham, G. Whittaker, and M. Straus for influenza A virus. This work was supported in part by grants from the National Institutes of Health (AI120701, AI138570 and AI126814 to AA; AI129422 and AI138497 to AA and WH, and AI137822 to WH), a Careers in Immunology Fellowship from the American Association of Immunologists (to WH), a Pilot Grant from the Center for Experimental Infectious Disease Research (funded by NIH P30GM110760), the Faculty Development Program and an award from Competitive Research Programs of the Louisiana State University (to WH).
Publisher Copyright:
© 2007 - 2018 Frontiers Media S.A.
PY - 2018/11/19
Y1 - 2018/11/19
N2 - 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.
AB - 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.
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U2 - 10.3389/fimmu.2018.02625
DO - 10.3389/fimmu.2018.02625
M3 - Article
C2 - 30510554
AN - SCOPUS:85057388910
SN - 1664-3224
VL - 9
JO - Frontiers in immunology
JF - Frontiers in immunology
IS - NOV
M1 - 2625
ER -