A key role for ICAM-I in generating effector cells mediating inflammatory responses

Stephanie A. Camacho, William R. Heath, Francis R. Carbone, Nora E Sarvetnick, Agnes LeBon, Lars Karlsson, Per A. Peterson, Susan R. Webb

Research output: Contribution to journalArticle

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Abstract

We investigated how the accessory molecule interactions encountered during T cell priming influence T cell-mediated destruction of insulin-producing β cells and lead to type I diabetes. T cell receptor (TCR)-transgenic CD4+ T cells were primed under controlled conditions in vitro before being adoptively transferred into transgenic recipients expressing membrane ovalbumin under the control of the rat insulin promoter (RIP-mOVA). During priming, antigen-presenting cell expression of B7-1 without intracellular adhesion molecule I (ICAM-1) led to the generation of effector cells that migrated to the pancreata of RIP-mOVA recipients but did not cause diabetes. In contrast, when T cells were primed with APCs expressing both B7-1 and ICAM-1, pronounced destruction of β cells and a rapid onset of diabetes were observed. Pathogenicity was associated with T cell production of the macrophage-attracting chemokines CCL3 and CCL4. Thus, interactions of lymphocyte function-associated antigen I with ICAM-1 during priming induce both qualitative and quantitative alterations in T effector function and induce potentially autodestructive responses.

Original languageEnglish (US)
Pages (from-to)523-529
Number of pages7
JournalNature Immunology
Volume2
Issue number6
DOIs
StatePublished - Jun 1 2001

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T-Lymphocytes
Intercellular Adhesion Molecule-1
Chemokine CCL4
Insulin
Chemokine CCL3
Ovalbumin
Antigen-Presenting Cells
T-Cell Antigen Receptor
Type 1 Diabetes Mellitus
Virulence
Pancreas
Macrophages
Lymphocytes
Membranes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Camacho, S. A., Heath, W. R., Carbone, F. R., Sarvetnick, N. E., LeBon, A., Karlsson, L., ... Webb, S. R. (2001). A key role for ICAM-I in generating effector cells mediating inflammatory responses. Nature Immunology, 2(6), 523-529. https://doi.org/10.1038/88720

A key role for ICAM-I in generating effector cells mediating inflammatory responses. / Camacho, Stephanie A.; Heath, William R.; Carbone, Francis R.; Sarvetnick, Nora E; LeBon, Agnes; Karlsson, Lars; Peterson, Per A.; Webb, Susan R.

In: Nature Immunology, Vol. 2, No. 6, 01.06.2001, p. 523-529.

Research output: Contribution to journalArticle

Camacho, SA, Heath, WR, Carbone, FR, Sarvetnick, NE, LeBon, A, Karlsson, L, Peterson, PA & Webb, SR 2001, 'A key role for ICAM-I in generating effector cells mediating inflammatory responses', Nature Immunology, vol. 2, no. 6, pp. 523-529. https://doi.org/10.1038/88720
Camacho, Stephanie A. ; Heath, William R. ; Carbone, Francis R. ; Sarvetnick, Nora E ; LeBon, Agnes ; Karlsson, Lars ; Peterson, Per A. ; Webb, Susan R. / A key role for ICAM-I in generating effector cells mediating inflammatory responses. In: Nature Immunology. 2001 ; Vol. 2, No. 6. pp. 523-529.
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