title: Tumor necrosis factor (TNF) receptor expression in T lymphocytes. Differential regulation of the type I TNF receptor during activation of resting and effector T cells.
abstract: The expression of TNF-alpha receptors (TNFR) was examined on a CD4+ T cell hybridoma, transformed T cell lines, CTL clones, and activated T cells from peripheral blood to determine the basis of the immunomodulatory activity of TNF on T cell function. Analyses by ligand cross-linking and competitive binding assays with mAb to the 80-kDa receptor (TNFR-I), demonstrated that the TNFR-I was the predominant receptor expressed on activated CD4+ and CD8+ T cell subsets. However, on T cell leukemic lines, a second, non-TNFR-I binding site was identified, most likely the 55-kDa form (TNFR-II). Additional subsets of T cells were readily distinguished by their expression of TNFR-I and related members of the TNFR gene family (CD40 and CD27). Expression of the TNFR-I was dependent upon the state of T cell activation. Signaling through the TCR for Ag or IL-2R was sufficient to induce TNFR mRNA and protein expression in resting T cells. Multiple sizes of TNFR-I transcripts were detected during T cell activation; however, biosynthetic studies showed these multiple species encode a single protein of 80 kDa. These results, combined with the known ability of TNF to induce IL-2R expression, indicate that TNF and IL-2 form a reciprocating receptor amplification circuit. In contrast, differentiated effector T cells triggered through the TCR or protein kinase C initiated a rapid down-regulation (transmodulation) of the TNFR-I that preceded TNF or lymphotoxin secretion. The mechanism of transmodulation involved proteolytic processing of the mature 80-kDa receptor releasing a soluble 40-kDa fragment. This indicates that a TNF autocrine loop is not likely to form during the response of an effector T cell. Collectively, these results suggest that transcriptional and post-translational modification of the TNFR-I are important control points regulating the expression of this receptor during T cell activation.
authors.affiliation: Division of Biomedical Sciences, University of California, Riverside 92521.
authors.forename: C F
authors.initials: CF
authors.lastname: Ware
authors.forename: P D
authors.initials: PD
authors.lastname: Crowe
authors.forename: T L
authors.initials: TL
authors.lastname: Vanarsdale
authors.forename: J L
authors.initials: JL
authors.lastname: Andrews
authors.forename: M H
authors.initials: MH
authors.lastname: Grayson
authors.forename: R
authors.initials: R
authors.lastname: Jerzy
authors.forename: C A
authors.initials: CA
authors.lastname: Smith
authors.forename: R G
authors.initials: RG
authors.lastname: Goodwin
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002478:Cells, Cultured; D008213:Lymphocyte Activation; D011233:Precipitin Tests; D051381:Rats; D011956:Receptors, Cell Surface / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D018124:Receptors, Tumor Necrosis Factor; D013601:T-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D011956:Receptors, Cell Surface; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha