Gene expression of Foxp3+CD8+ Tregs induced with or without laminin α5

Foxp3+CD8+ regulatory T cells (CD8 Tregs) help to establish immune tolerance in models of chronic inflammation and antigen stimulation, such as graft versus host disease and chronic infections. However, the elements contributing to CD8 Treg induction remain obscure. In this study, we found that laminin α5 enhanced CD8 Treg inducation from mouse naive T cells stimulated with a combination of anit-CD3/anti-CD28/IL-2/TGFβ. While, the suppressive ability of CD8 Tregs induced with laminin α5 was reduced by 23.8% compared to these induced without laminin α5; the cytotoxic ability of CD8 Tregs induced with laminin α5 was significant reduced (more than 64%) compared to these induced without laminin α5. Mechanistically, laminin α5 was invovled in modulating both TCR signaling and cytokine responses during induction of CD8 Tregs. Laminin α5 inihbited IFNg and TNFa expression by CD8 T cells, which further enhanced Foxp3+CD8+ Treg induction. Laminin α5-Itga6 enhanced TCR signaling by promoting activation of the LAT/Zap70/PLCγ1 pathways.