Details

Autor(en) / Beteiligte

• Ogawa, Shu-hei
• Nagamatsu, Go
• Watanabe, Masashi
• Watanabe, Shiho
• Hayashi, Tomohito
• Horita, Shigeru
• Nitta, Kosaku
• Nihei, Hiroshi
• Tezuka, Katsunari
• Abe, Ryo

Titel

Opposing Effects of Anti-Activation-Inducible Lymphocyte- Immunomodulatory Molecule/Inducible Costimulator Antibody on the Development of Acute Versus Chronic Graft-Versus-Host Disease

Ist Teil von

• The Journal of immunology (1950), 2001-11, Vol.167 (10), p.5741-5748

Ort / Verlag

United States: Am Assoc Immnol

Erscheinungsjahr

2001

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.