Modulation of human t cell activation and tolerance induction by a monoclonal antibody to ICAM-1

Laurie S. Davis, Peter E. Lipskv

Research output: Contribution to journalArticle

Abstract

Initially, T cells interact with antigen presenting cells (APC) via LFA-1/ICAM-l. Previously, we have shown that recombinant ICAM-1 was able to co-stimulate anti-CD3 monoclonal antibody (mAb) induced IL-2 production and DNA synthesis in freshly isolated human peripheral blood T cells. ICAM-1 co-stimulated both CD4+ naive (CD45RA+) and memory (CD45RO+) T cell subsets. A mAb to ICAM-1, BIRR1, blocked LFA1/ICAM-l interactions in both antigen and mitogen stimulated cultures. Anti-ICAM-1 mAb blocked IL-2 production but not expression of activation markers including CD69, CD30, and CD25 on antigen-stimulated T cell lines. Activation markers were partially blocked in cultures of freshly isolated T cells stimulated with OKT3-pulsed accessory cells. In addition, the LFA-l/ICAM-1 interaction was shown to be critical for the prevention of anergy. This finding was supported by previous studies of rheumatoid arthritis patients treated with the anti-ICAM-1 mAb. These patients exhibited a hyporesponsiveness defined as a defect in IL-2 production that was sustained long after the mAb was detectable in the serum or on peripheral blood cells. These studies suggest an important role for CD54 in antigen responses of resting T cells and modulation of function of recently activated memory T cells that have increased numbers of adhesion molecules. Thus. mAb to ICAM-1 have the Dotential to downreeulate IL-2 production selectively.

Original languageEnglish (US)
JournalFASEB Journal
Volume10
Issue number6
StatePublished - 1996

Fingerprint

T-cells
Intercellular Adhesion Molecule-1
monoclonal antibodies
T-lymphocytes
Chemical activation
Monoclonal Antibodies
Modulation
interleukin-2
Interleukin-2
T-Lymphocytes
cells
blood cells
antigens
Antigens
Blood
Blood Cells
Data storage equipment
Muromonab-CD3
Interleukin-2 Receptor alpha Subunit
Lymphocyte Function-Associated Antigen-1

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Modulation of human t cell activation and tolerance induction by a monoclonal antibody to ICAM-1. / Davis, Laurie S.; Lipskv, Peter E.

In: FASEB Journal, Vol. 10, No. 6, 1996.

Research output: Contribution to journalArticle

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