Enhanced suppressive phenotype of Tim-3+ Treg during chronic infection

Abstract

Abstract T cell (or transmembrane) immunoglobulin and mucin-domain containing protein-3 (Tim-3) is a cell-surface protein expressed during T cell exhaustion, a process that leads to a progressive loss of effector function due to chronic T cell receptor (TCR) stimulation. In humans, Tim-3 expression has also been found to be increased on Treg isolated from tumors and during chronic viral infection. However, the role of Tim-3 on Treg during chronic viral infection remains largely unknown. Our main hypothesis is that Tim-3 expression on Treg will increase their proliferation and suppressive capacity during LCMV infection. To test this, we infected C57/BL6 mice for 30 days with LCMV clone-13, a well-established model for chronic infection. We found that at 16 days post-infection there is an increase in the frequency and number of Tim-3+Foxp3+ Treg in the spleen. By flow cytometry we found that Tim3+ Treg have increased expression of CD44, Ki67, Helios, ICOS, KLRG-1, CD39 and CD25, compared with Tim-3− Treg. Therefore, our data suggest that Tim-3+ Treg have a phenotype associated with higher activation, proliferation and suppression during chronic infection. Understanding the contributions of Tim-3 to Treg activation and function may provide new insights into the role of Tim-3 during disease progression and response to therapy.