Distinct functions of autoreactive memory and effector CD4+ T cells in experimental autoimmune encephalomyelitis

Wassim Elyaman, Pia Kivisäkk, Jay Reddy, Tanuja Chitnis, Khadir Raddassi, Jaime Imitola, Elizabeth Bradshaw, Vijay K. Kuchroo, Hideo Yagita, Mohamed H. Sayegh, Samia J. Khoury

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

The persistence of human autoimmune diseases is thought to be mediated predominantly by memory T cells. We investigated the phenotype and migration of memory versus effector T cells in vivo in experimental autoimmune encephalomyelitis (EAE). We found that memory CD4+ T cells up-regulated the activation marker CD44 as well as CXCR3 and ICOS, proliferated more and produced more interferon-γ and less interleukin-17 compared to effector T cells. Moreover, adoptive transfer of memory T cells into T cell receptor (TCR)αβ-/- recipients induced more severe disease than did effector CD4+ T cells with marked central nervous system inflammation and axonal damage. The uniqueness of disease mediated by memory T cells was confirmed by the differential susceptibility to immunomodulatory therapies in vivo. CD28-B7 T cell costimulatory signal blockade by CTLA4Ig suppressed effector cell-mediated EAE but had minimal effects on disease induced by memory cells. In contrast, ICOS-B7h blockade exacerbated effector T cell-induced EAE but protected from disease induced by memory T cells. However, blockade of the OX40 (CD134) costimulatory pathway ameliorated disease mediated by both memory and effector T cells. Our data extend the understanding of the pathogenicity of autoreactive memory T cells and have important implications for the development of novel therapies for human autoimmune diseases.

Original languageEnglish (US)
Pages (from-to)411-422
Number of pages12
JournalAmerican Journal of Pathology
Volume173
Issue number2
DOIs
StatePublished - Aug 2008

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Elyaman, W., Kivisäkk, P., Reddy, J., Chitnis, T., Raddassi, K., Imitola, J., Bradshaw, E., Kuchroo, V. K., Yagita, H., Sayegh, M. H., & Khoury, S. J. (2008). Distinct functions of autoreactive memory and effector CD4+ T cells in experimental autoimmune encephalomyelitis. American Journal of Pathology, 173(2), 411-422. https://doi.org/10.2353/ajpath.2008.080142