ILA, a member of the human nerve growth factor/tumor necrosis factor receptor family, regulates T-lymphocyte proliferation and survival.
ILA, a gene induced by lymphocyte activation, is a member of the human nerve growth factor tumor necrosis factor receptor family and the human homologue of murine 4-1BB. The present study analyzed the role of ILA in the regulation of human peripheral blood T-lymphocyte function. Antibodies raised against different fusion proteins recognized ILA on activated lymphocytes. These antibodies significantly increased anti-CD3--induced T-lymphocyte proliferation. When anti-CD3--stimulated cells were incubated on ILA-expressing CHO cells, proliferation was inhibited. CHO cells transfected with a control construct and not expressing ILA did not reduce T-cell proliferation. A purified fusion protein containing the extracellular domain of ILA and the constant domain of human IgG (ILA-IgG) also inhibited lymphocyte proliferation. Results obtained by 3H-thymidine incorporation were confirmed by cell cycle analysis that showed a decrease in the number of lymphocytes in S phase. Lymphocyte morphology in cultures with ILA-expressing CHO cells was suggestive of apoptosis. Flow cytometry on propidium iodide-stained cells showed a time-dependent increase in the number of hypodiploid apoptotic cells when lymphocytes were cultured on ILA-expressing CHO cells. Internucleosomal DNA cleavage was seen in these cultures, but not in the presence of ILA-negative CHO cells. Studies on the mechanism by which ILA regulates T-cell function showed that ILA-IgG inhibited anti-CD3-induced T-cell proliferation when presented in immobilized but not in soluble form. These results suggest that ILA may act by cross-linking its ligand and thereby inhibit T-cell proliferation.
Schwarz
H
H
Sam and Rose Stein Institute for Research on Aging, University of California at San Diego, La Jolla, CA, USA.
Blanco
F J
FJ
von Kempis
J
J
Valbracht
J
J
Lotz
M
M
D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D002455:Cell Division; D002470:Cell Survival; D006224:Cricetinae; D006801:Humans; D008969:Molecular Sequence Data; D018121:Receptors, Cytokine / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism
C084945:ILA receptor; D018121:Receptors, Cytokine