Semaphorin 6D regulates the late phase of CD4+ T cell primary immune responses.

Published

Journal Article

The semaphorin and plexin family of ligand and receptor proteins provides important axon guidance cues required for development. Recent studies have expanded the role of semaphorins and plexins in the regulation of cardiac, circulatory and immune system function. Within the immune system, semaphorins and plexins regulate cell-cell interactions through a complex network of receptor and ligand pairs. Immune cells at different stages of development often express multiple semaphorins and plexins, leading to multivariate interactions, involving more than one ligand and receptor within each functional group. Because of this complexity, the significance of semaphorin and plexin regulation on individual immune cell types has yet to be fully appreciated. In this work, we examined the regulation of T cells by semaphorin 6D. Both in vitro and in vivo T cell stimulation enhanced semaphorin 6D expression. However, semaphorin 6D was only expressed by a majority of T cells during the late phases of activation. Consequently, the targeted disruption of semaphorin 6D receptor-ligand interactions inhibited T cell proliferation at late but not early phases of activation. This proliferation defect was associated with reduced linker of activated T cells protein phosphorylation, which may reflect semaphorin 6D regulation of c-Abl kinase activity. Semaphorin 6D disruption also inhibited expression of CD127, which is required during the multiphase antigen-presenting cell and T cell interactions leading to selection of long-lived lymphocytes. This work reveals a role for semaphorin 6D as a regulator of the late phase of primary immune responses.

Full Text

Duke Authors

Cited Authors

  • O'Connor, BP; Eun, S-Y; Ye, Z; Zozulya, AL; Lich, JD; Moore, CB; Iocca, HA; Roney, KE; Holl, EK; Wu, QP; van Deventer, HW; Fabry, Z; Ting, JP-Y

Published Date

  • September 2, 2008

Published In

Volume / Issue

  • 105 / 35

Start / End Page

  • 13015 - 13020

PubMed ID

  • 18728195

Pubmed Central ID

  • 18728195

Electronic International Standard Serial Number (EISSN)

  • 1091-6490

Digital Object Identifier (DOI)

  • 10.1073/pnas.0803386105

Language

  • eng

Conference Location

  • United States