Mesenchymal Stromal Cells Suppress T-Cell-Mediated Delayed-Type Hypersensitivity via ALCAM-CD6 Interaction

Author:

Cho WonKyung J1ORCID,Mittal Sharad K1,Chauhan Sunil K1ORCID

Affiliation:

1. Schepens Eye Research Institute of Mass Eye and Ear, Harvard Medical School , Boston , MA , USA

Abstract

AbstractMounting evidence suggests mesenchymal stromal cells (MSCs) suppress CD4+ T-cell activation, but whether MSCs directly regulate activation and expansion of allogeneic T cells has not been fully deciphered. Here, we identified that both human and murine MSCs constitutively express ALCAM, a cognate ligand for CD6 receptors on T cells, and investigated its immunomodulatory function using in vivo and in vitro experiments. Our controlled coculture assays demonstrated that ALCAM-CD6 pathway is critical for MSCs to exert its suppressive function on early CD4+CD25− T-cell activation. Moreover, neutralizing ALCAM or CD6 results in the abrogation of MSC-mediated suppression of T-cell expansion. Using a murine model of delayed-type hypersensitivity response to alloantigen, we show that ALCAM-silenced MSCs lose the capacity to suppress the generation of alloreactive IFNγ-secreting T cells. Consequently, MSCs, following ALCAM knockdown, failed to prevent allosensitization and alloreactive T-cell-mediated tissue damage.

Funder

National Institutes of Health

Publisher

Oxford University Press (OUP)

Subject

Cell Biology,Developmental Biology,General Medicine

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