TY - JOUR
T1 - Surface density expression of the leukocyte-associated Ig-like receptor-1 is directly related to inhibition of human T-cell functions
AU - Saverino, Daniele
AU - Fabbi, Marina
AU - Merlo, Andrea
AU - Ravera, Giambattista
AU - Grossi, Carlo E.
AU - Ciccone, Ermanno
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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.
KW - Cytokines
KW - Inhibitory receptors
KW - LAIR-1
KW - T lymphocytes
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U2 - 10.1016/S0198-8859(02)00409-3
DO - 10.1016/S0198-8859(02)00409-3
M3 - Article
C2 - 12072189
AN - SCOPUS:0035985415
VL - 63
SP - 534
EP - 546
JO - Human Immunology
JF - Human Immunology
SN - 0198-8859
IS - 7
ER -