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-gamma production. In contrast, LAIR-1 crosslinking induces secretion of transforming growth factor beta. 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.
Saverino
Daniele
D
Department of Experimental Medicine, Human Anatomy Section, University of Genova, Genova, Italy.
Fabbi
Marina
M
Merlo
Andrea
A
Ravera
Giambattista
G
Grossi
Carlo E
CE
Ciccone
Ermanno
E
D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002455:Cell Division; D002462:Cell Membrane / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D011971:Receptors, Immunologic / Q000096:biosynthesis* / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D014373:Tuberculin / Q000276:immunology
D017252:CD3 Complex; D007376:Interleukin-2; D011971:Receptors, Immunologic; D016212:Transforming Growth Factor beta; D014373:Tuberculin; C108073:leukocyte-associated immunoglobulin-like receptor 1; D007371:Interferon-gamma