CD30/CD30 ligand (CD153) interaction regulates CD4+ T cell-mediated graft-versus-host disease

Bruce R. Blazar, Robert B Levy, Tak W. Mak, Angela Panoskaltsis-Mortari, Hiromi Muta, Monica Jones, Melinda Roskos, Jonathan S. Serody, Hideo Yagita, Eckhard R. Podack, Patricia A. Taylor

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

CD30, a TNFR family member, is expressed on activated CD4+ and CD8+ T cells and B cells and is a marker of Hodgkin's lymphoma; its ligand, CD30L (CD153) is expressed by activated CD4+ and CD8 + T cells, B cells, and macrophages. Signaling via CD30 can lead to proliferation or cell death. CD30-deficient (-/-) mice have impaired thymic negative selection and increased autoreactivity. Although human alloreactive T cells preferentially reside within the CD30+ T cell subset, implicating CD30 as a regulator of T cell immune responses, the role of CD30/CD153 in regulating graft-vs-host disease (GVHD) has not been reported. We used a neutralizing anti-CD153 mAb, CD30-/- donor mice, and generated CD153-/- recipient mice to analyze the effect of CD30/CD153 interaction on GVHD induction. Our data indicate that the CD30/CD153 pathway is a potent regulator of CD4+, but not CD8+, T cell-mediated GVHD. Although blocking CD30/CD153 interactions in vivo did not affect alloreactive CD4+ T cell proliferation or apoptosis, a substantial reduction in donor CD4+ T cell migration into the gastrointestinal tract was readily observed with lesser effects in other GVHD target organs. Blockade of the CD30/CD153 pathway represents a new approach for preventing CD4+ T cell-mediated GVHD.

Original languageEnglish
Pages (from-to)2933-2941
Number of pages9
JournalJournal of Immunology
Volume173
Issue number5
StatePublished - Sep 1 2004

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CD30 Ligand
Graft vs Host Disease
T-Lymphocytes
B-Lymphocytes
T-Lymphocyte Subsets
Hodgkin Disease
Cell Movement
Gastrointestinal Tract
Cell Death
Macrophages
Cell Proliferation

ASJC Scopus subject areas

  • Immunology

Cite this

Blazar, B. R., Levy, R. B., Mak, T. W., Panoskaltsis-Mortari, A., Muta, H., Jones, M., ... Taylor, P. A. (2004). CD30/CD30 ligand (CD153) interaction regulates CD4+ T cell-mediated graft-versus-host disease. Journal of Immunology, 173(5), 2933-2941.

CD30/CD30 ligand (CD153) interaction regulates CD4+ T cell-mediated graft-versus-host disease. / Blazar, Bruce R.; Levy, Robert B; Mak, Tak W.; Panoskaltsis-Mortari, Angela; Muta, Hiromi; Jones, Monica; Roskos, Melinda; Serody, Jonathan S.; Yagita, Hideo; Podack, Eckhard R.; Taylor, Patricia A.

In: Journal of Immunology, Vol. 173, No. 5, 01.09.2004, p. 2933-2941.

Research output: Contribution to journalArticle

Blazar, BR, Levy, RB, Mak, TW, Panoskaltsis-Mortari, A, Muta, H, Jones, M, Roskos, M, Serody, JS, Yagita, H, Podack, ER & Taylor, PA 2004, 'CD30/CD30 ligand (CD153) interaction regulates CD4+ T cell-mediated graft-versus-host disease', Journal of Immunology, vol. 173, no. 5, pp. 2933-2941.
Blazar BR, Levy RB, Mak TW, Panoskaltsis-Mortari A, Muta H, Jones M et al. CD30/CD30 ligand (CD153) interaction regulates CD4+ T cell-mediated graft-versus-host disease. Journal of Immunology. 2004 Sep 1;173(5):2933-2941.
Blazar, Bruce R. ; Levy, Robert B ; Mak, Tak W. ; Panoskaltsis-Mortari, Angela ; Muta, Hiromi ; Jones, Monica ; Roskos, Melinda ; Serody, Jonathan S. ; Yagita, Hideo ; Podack, Eckhard R. ; Taylor, Patricia A. / CD30/CD30 ligand (CD153) interaction regulates CD4+ T cell-mediated graft-versus-host disease. In: Journal of Immunology. 2004 ; Vol. 173, No. 5. pp. 2933-2941.
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