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

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.