Opposing effects of anti-activation-inducible lymphocyte-immunomodulatory molecule/inducible costimulator antibody on the development of acute versus chronic graft-versus-host disease.
The functional role of inducible costimulator (ICOS)-mediated costimulation was examined in an in vivo model of alloantigen-driven Th1 or Th2 cytokine responses, the parent-into-F(1) model of acute or chronic graft-vs-host disease (GVHD), respectively. When the Ab specific for mouse ICOS was injected into chronic GVHD-induced mice, activation of B cells, production of autoantibody, and development of glomerulonephritis were strongly suppressed. In contrast, the same treatment enhanced donor T cell chimerism and host B cell depletion in acute GVHD induced host mice. Blocking of B7-CD28 interaction by injection of anti-B7-1 and anti-B7-2 Abs inhibited both acute and chronic GVHD. These observations clearly indicate that the costimulatory signal mediated by CD28 caused the initial allorecognition resulting in the clonal expansion of alloreactive T cells, whereas the costimulatory signal mediated by ICOS played a critical role in the functional differentiation and manifestation of alloreactive T cells. Furthermore, treatment with anti-ICOS Ab selectively suppresses Th2-dominant autoimmune disease.
Ogawa
S
S
Division of Immunobiology, Research Institutes of Biological Sciences, Science University of Tokyo, Chiba, Japan.
Nagamatsu
G
G
Watanabe
M
M
Watanabe
S
S
Hayashi
T
T
Horita
S
S
Nitta
K
K
Nihei
H
H
Tezuka
K
K
Abe
R
R
D000208:Acute Disease; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D001323:Autoantibodies / Q000096:biosynthesis; D002478:Cells, Cultured; D002908:Chronic Disease; D016207:Cytokines / Q000096:biosynthesis; D003601:Cytotoxicity Tests, Immunologic; D005260:Female; D005921:Glomerulonephritis / Q000276:immunology / Q000473:pathology; D006086:Graft vs Host Disease / Q000276:immunology* / Q000473:pathology; D007136:Immunoglobulins / Q000096:biosynthesis; D060889:Inducible T-Cell Co-Stimulator Protein; D007267:Injections; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D001323:Autoantibodies; D016207:Cytokines; C556694:Icos protein, mouse; D007136:Immunoglobulins; D060889:Inducible T-Cell Co-Stimulator Protein