TY - JOUR
T1 - CD30/CD30 ligand (CD153) interaction regulates CD4+ T cell-mediated graft-versus-host disease
AU - Blazar, Bruce R.
AU - Levy, Robert B.
AU - Mak, Tak W.
AU - Panoskaltsis-Mortari, Angela
AU - Muta, Hiromi
AU - Jones, Monica
AU - Roskos, Melinda
AU - Serody, Jonathan S.
AU - Yagita, Hideo
AU - Podack, Eckhard R.
AU - Taylor, Patricia A.
PY - 2004/9/1
Y1 - 2004/9/1
N2 - 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.
AB - 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.
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U2 - 10.4049/jimmunol.173.5.2933
DO - 10.4049/jimmunol.173.5.2933
M3 - Article
C2 - 15322151
AN - SCOPUS:4344659974
SN - 0022-1767
VL - 173
SP - 2933
EP - 2941
JO - Journal of Immunology
JF - Journal of Immunology
IS - 5
ER -