A Novel Role for the Semaphorin Sema4D in the Induction of Allo-responses

Raimon Duran-Struuck, Isao Tawara, Kathi Lowler, Shawn G. Clouthier, Elizabeth Weisiger, Clare Rogers, Gary Luker, Atsushi Kumanogoh, Chen Liu, James L.M. Ferrara, Pavan Reddy

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


Sema4D (CD100), a member of the neuro-semaphorin family of proteins, has recently been shown to play a role in modulating certain immune responses. We tested the requirement of Sema4D expression on T cells in the induction of T cell allo-immune responses. Sema4D-/- T cells showed reduced expansion in vitro upon stimulation with allo-geneic antigen presenting cells (APCs) when compared to wild-type (wt) T cells. Similar in vitro results were observed using anti-Sema4D mAbs. Further studies demonstrated that the reduced proliferation was not due to intrinsic T cell defects, and that the cytotoxic functions were preserved. After allo-geneic bone marrow transplant (BMT), recipients of Sema4D-/- T cells showed reduced mortality and graft-versus-host disease (GVHD) target organ damage. Allo-geneic dendritic cells (DCs) cocultured with Sema4D-/- responder T cells secreted less TNF-α and IL-12p70 compared to wt T cells. Similar reduction of DC function was observed with anti-Sema4D mAbs. Given the preservation of CTL function we evaluated graft-versus-leukemia (GVL) responses. When BALB/c recipient mice were challenged with the P815 murine mastocytoma cell line (H2d) the recipients of allo-geneic Sema4D-/- B6 T cells showed a significant improvement in tumor free survival when compared to syngeneic recipients, thus demonstrating preservation of GVL, albeit of a lesser magnitude than allo-geneic wt T cells. In summary, Sema4D plays a significant role in mediating in vitro and in vivo allo-geneic responses by modulating T cell-APC interactions.

Original languageEnglish
Pages (from-to)1294.e1-1294.e11
JournalBiology of Blood and Marrow Transplantation
Issue number11
StatePublished - Nov 2007
Externally publishedYes


  • BMT
  • CD100
  • Cytokines
  • GVHD
  • T cells


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