Surface density expression of the leukocyte-associated Ig-like receptor-1 is directly related to inhibition of human T-cell functions

Daniele Saverino, Marina Fabbi, Andrea Merlo, Giambattista Ravera, Carlo E. Grossi, Ermanno Ciccone

Research output: Contribution to journalArticlepeer-review

Abstract

The relevance of inhibitory receptors that downregulate T-cell functions, such as CD152 (CTLA-4) and CD85j, have been extensively analyzed. This study will show that leukocyte-associated Ig-like receptor-1 (LAIR-1) acts as an inhibitory receptor for antigen-specific human effector T cells. To this end 28 CD8+ and 22 CD4+ T-cell clones were analyzed. LAIR-1 activity appears to be clonally distributed among T-cell clones and inhibition of T lymphocyte functions ranges from 4% to 49% in a redirected killing assay. This inhibitory function, although less efficient than that exerted by other inhibitory receptors expressed by T cells (i.e., CD152 and CD85j), downregulates the cytotoxic activity of CD8+ T lymphocytes, both in a CD3-mediated and in an antigen-specific system. Furthermore, LAIR-1 inhibits the proliferative response of CD4+ T lymphocytes to recall antigens and in CD3 stimulation. LAIR-1 also modulates cytokine production, downregulating IL-2 and IFN-γ production. In contrast, LAIR-1 crosslinking induces secretion of transforming growth factor β. This study will also demonstrate that a direct relationship exists between surface density expression of LAIR-1 molecules and their ability to modulate CD3-mediated activation of both CD8+ and CD4+ T-cell clones.

Original languageEnglish
Pages (from-to)534-546
Number of pages13
JournalHuman Immunology
Volume63
Issue number7
DOIs
Publication statusPublished - 2002

Keywords

  • Cytokines
  • Inhibitory receptors
  • LAIR-1
  • T lymphocytes

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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