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- Publisher Website: 10.1182/blood-2004-10-3869
- Scopus: eid_2-s2.0-17044374080
- PMID: 15618467
- WOS: WOS:000228344500060
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Article: Targeting of inducible costimulator (ICOS) expressed on alloreactive T cells down-regulates graft-versus-host disease (GVHD) and facilitates engraftment of allogeneic bone marrow (BM)
Title | Targeting of inducible costimulator (ICOS) expressed on alloreactive T cells down-regulates graft-versus-host disease (GVHD) and facilitates engraftment of allogeneic bone marrow (BM) |
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Authors | |
Issue Date | 2005 |
Citation | Blood, 2005, v. 105, n. 8, p. 3372-3380 How to Cite? |
Abstract | Inducible costimulator (ICOS), a CD28/ cytotoxic T lymphocyte antigen 4 (CTLA-4) family member, is expressed on activated T cells. ICOS ligand, a B7 family member, is constitutively expressed on B cells, macrophages, and dendritic cells and is up-regulated on antigen-presenting cells (APCs) and some nonlymphoid tissues by tumor necrosis factor α (TNFα) or lipopolysaccharide (LPS). Thus, ICOS: ICOS ligand (ICOSL) blockade could reduce alloreactive T cell-APC interactions responsible for graft-versus-host disease (GVHD) and bone marrow (BM) graft rejection. ICOS blockade, achieved with ICOS-/- mice or anti-ICOS monoclonal antibody (mAb) administration, resulted in significant inhibition of GVHD in multiple strain combinations whether mediated by CD4+ and/or CD8+ T cells, alloantigen-specific T-cell receptor (TCR) transgenic (Tg) T cells, or CD28-, T helper 1 (Th1)-, or Th2-deficient T cells. Anti-ICOS significantly delayed GVHD mortality even when mAb infusions were delayed until day 5 after transplantation. ICOS blockade reduced the number of alloantigen-specific effector cells but did not prevent their activation. Imaging of green fluorescent protein-positive (GFP+) effectors indicated that ICOS blockade inhibited expansion of GVHD-causing effector T cells in secondary lymphoid and GVHD target organs. Engraftment rates were significantly higher in ICOS-/- versus wild-type (WT) mice receiving allogeneic BM, and ICOS blockade significantly inhibited expansion of host antidonor alloantigen-specific BM graft-rejecting T cells. These data suggest that the ICOS pathway may be a beneficial therapeutic target for GVHD inhibition, GVHD therapy, and BM graft promotion. © 2005 by The American Society of Hematology. |
Persistent Identifier | http://hdl.handle.net/10722/291708 |
ISSN | 2023 Impact Factor: 21.0 2023 SCImago Journal Rankings: 5.272 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Taylor, Patricia A. | - |
dc.contributor.author | Panoskaltsis-Mortari, Angela | - |
dc.contributor.author | Freeman, Gordon J. | - |
dc.contributor.author | Sharpe, Arlene H. | - |
dc.contributor.author | Noelle, Randolph J. | - |
dc.contributor.author | Rudensky, Alexander Y. | - |
dc.contributor.author | Mak, Tak W. | - |
dc.contributor.author | Serody, Jonathan S. | - |
dc.contributor.author | Blazar, Bruce R. | - |
dc.date.accessioned | 2020-11-17T14:54:56Z | - |
dc.date.available | 2020-11-17T14:54:56Z | - |
dc.date.issued | 2005 | - |
dc.identifier.citation | Blood, 2005, v. 105, n. 8, p. 3372-3380 | - |
dc.identifier.issn | 0006-4971 | - |
dc.identifier.uri | http://hdl.handle.net/10722/291708 | - |
dc.description.abstract | Inducible costimulator (ICOS), a CD28/ cytotoxic T lymphocyte antigen 4 (CTLA-4) family member, is expressed on activated T cells. ICOS ligand, a B7 family member, is constitutively expressed on B cells, macrophages, and dendritic cells and is up-regulated on antigen-presenting cells (APCs) and some nonlymphoid tissues by tumor necrosis factor α (TNFα) or lipopolysaccharide (LPS). Thus, ICOS: ICOS ligand (ICOSL) blockade could reduce alloreactive T cell-APC interactions responsible for graft-versus-host disease (GVHD) and bone marrow (BM) graft rejection. ICOS blockade, achieved with ICOS-/- mice or anti-ICOS monoclonal antibody (mAb) administration, resulted in significant inhibition of GVHD in multiple strain combinations whether mediated by CD4+ and/or CD8+ T cells, alloantigen-specific T-cell receptor (TCR) transgenic (Tg) T cells, or CD28-, T helper 1 (Th1)-, or Th2-deficient T cells. Anti-ICOS significantly delayed GVHD mortality even when mAb infusions were delayed until day 5 after transplantation. ICOS blockade reduced the number of alloantigen-specific effector cells but did not prevent their activation. Imaging of green fluorescent protein-positive (GFP+) effectors indicated that ICOS blockade inhibited expansion of GVHD-causing effector T cells in secondary lymphoid and GVHD target organs. Engraftment rates were significantly higher in ICOS-/- versus wild-type (WT) mice receiving allogeneic BM, and ICOS blockade significantly inhibited expansion of host antidonor alloantigen-specific BM graft-rejecting T cells. These data suggest that the ICOS pathway may be a beneficial therapeutic target for GVHD inhibition, GVHD therapy, and BM graft promotion. © 2005 by The American Society of Hematology. | - |
dc.language | eng | - |
dc.relation.ispartof | Blood | - |
dc.title | Targeting of inducible costimulator (ICOS) expressed on alloreactive T cells down-regulates graft-versus-host disease (GVHD) and facilitates engraftment of allogeneic bone marrow (BM) | - |
dc.type | Article | - |
dc.description.nature | link_to_OA_fulltext | - |
dc.identifier.doi | 10.1182/blood-2004-10-3869 | - |
dc.identifier.pmid | 15618467 | - |
dc.identifier.scopus | eid_2-s2.0-17044374080 | - |
dc.identifier.volume | 105 | - |
dc.identifier.issue | 8 | - |
dc.identifier.spage | 3372 | - |
dc.identifier.epage | 3380 | - |
dc.identifier.isi | WOS:000228344500060 | - |
dc.identifier.issnl | 0006-4971 | - |