CD30/CD30 ligand (CD153) interaction regulates CD4+ T cell-mediated graft-versus-host disease.
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.
Blazar
Bruce R
BR
Cancer Center and Department of Pediatrics, Division of Bone Marrow Transplantation, University of Minnesota, Minneapolis, MN 55455, USA. blaza001@tc.umn.edu
Levy
Robert B
RB
Mak
Tak W
TW
Panoskaltsis-Mortari
Angela
A
Muta
Hiromi
H
Jones
Monica
M
Roskos
Melinda
M
Serody
Jonathan S
JS
Yagita
Hideo
H
Podack
Eckhard R
ER
Taylor
Patricia A
PA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D016026:Bone Marrow Transplantation / Q000276:immunology; D053285:CD30 Ligand; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D006086:Graft vs Host Disease / Q000276:immunology / Q000378:metabolism* / Q000401:mortality; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D017730:Ki-1 Antigen / Q000276:immunology / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism*; D051379:Mice
D000911:Antibodies, Monoclonal; D053285:CD30 Ligand; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D017730:Ki-1 Antigen; D008562:Membrane Glycoproteins; C505774:TNFSF8 protein, human; C505775:Tnfsf8 protein, mouse