Identification of a novel inducible cell-surface ligand of CD5 on activated lymphocytes.

Abstract

SumlTlaryCD5 is a 67-kD glycoprotein that is expressed on most T lymphocytes and on a subset of mature B cells. Although its physiologic function is unknown, several lines of evidence suggest that CD5 may play a role in the regulation ofT cell activation and in T cell-antigen presenting cell interactions. Using a CDS-immunoglobulin fusion protein (CD5Rg, for receptorglobulin), we have uncovered a new CD5 ligand (CD5L) expressed on the surface of activated splenocytes. Stimulation of murine splenocytes with anti-CD3 and anti-CD28 antibodies induces transient expression of CD5L on B lymphocytes that lasts for "72 h. Binding of CD5Rg to activated splenocytes is trypsin-resistant and independent of divalent cations. However, it is pronase sensitive and dependent on N-linked glycosylation of CD5, since treatment of CD5Rg with PNGaseF or N-glycanase completely abrogates its ability to bind activated splenocytes. In addition to splenocytes, CD5L is expressed on activated murine T cell clones. Immunoprecipitation, antibody, and recombinant protein blocking studies indicate that CDSL is distinct from CD72, which has been proposed to be a CD5 ligand. To determine whether CD5-CD5L interaction might play a role in vivo, we tested the effect of CD5Rg in a murine model of antibody-mediated membranous glomerulonephritis. Injection of CD5Rg was found to abrogate development of the disease. Taken together, our results help identify a novel ligand of CD5 and propose a role for CD5 in the regulation of inmmne responses. C D5 is a 67-kD glycoprotein that is structurally related to the scavenger receptor cysteine-rich family (1), and expressed on thymocytes, T lymphocytes and subpopulations of mature and activated B cells. In particular, autoreactive B lymphocytes are observed to express CD5 (2) and, at least in the mouse, the development ofCD5 + B cells appears to be regulated in part by IL-10 (3). The precise physiologic function of CD5 has yet to be elucidated. CD5 may play a significant role in T lymphocyte activation, however, based on observations that anti-CD5 antibodies can augment T cell intracellular calcium concentration (4), proliferation (5, 6), and IL-2 release (7, 8). CD5 associates with the TCR ~ chain, and is rapidly phosphorylated after ligation of CD3/TCR (9, 10). Recently, deletion of the CD5 gene was shown to influence the development of thymocytes in transgenic mice (11). In vivo, down-modulation of CD5 by mAb induces T cell unresponsiveness, and is reported to prevent experimental autoimnmne encephalomyelitis in the rat (12). In addition, anti-CD5 antibody treatment has a partial therapeutic effect on collagen type II-induced arthritis in DBA/1 mice (13). Taken together, these studies suggest that CD5 may play an important role in transducing signals that are relevant to thymic development and to immune responses.Purified biotin-labeled CD5 has been proposed to bind CD72/Lyb-2 on both human and routine cells (14,15). CD72 is a type II glycoprotein of 42 kD that is costitutively expressed on all cells of the B ...

Frontline: Optimal T cell activation requires the engagement of CD6 and CD166

“…Proteins in this group can bind cell surface or soluble ligands. There are good molecular data showing that CD6 binds the cell surface protein, activated leukocyte cell adhesion molecule (ALCAM/CD166) [4] and preliminary data supporting the existence of cell surface ligands for WC1 [5] and CD5 [6][7][8]. In contrast, M130/CD163 binds the soluble complex, haptoglobin-hemoglobin [9].…”

Rescue of Tumor-Infiltrating Lymphocytes from Activation-Induced Cell Death Enhances the Antitumor CTL Response in CD5-Deficient Mice

“…Therefore, interaction of CD5 with its ligand does not seem to be necessary for TCR signaling inhibition. Various potential ligands for CD5 have been described (11)(12)(13)(14)(15), but the true identity of the physiologically relevant ligand remains to be determined. It has also been reported that conserved fungal components bind to membrane-bound CD5 to induce cytokine release and that a soluble CD5 ectodomain protects mice from zymosan-induced septic shocklike syndrome (16).…”

The Identification and Characterization of a Ligand for Bovine CD5

“…Independent studies aimed at characterizing the ligand for CD5 have demonstrated the ligand to be expressed on a variety of cell types (37)(38)(39)(40)(41)(42). Analysis of freshly isolated bovine PBMCs indicated that cells expressing low levels of CD5L in vivo were of an activated phenotype based on forward angle light scatter and were CD3 Ϫ , CD5 Ϫ , and IgM ϩ (data not shown).…”

“…However, recent studies have suggested that CD5 may bind to one or more alternative ligand(s). Using a CD5-huIgG1 fusion protein, Biancone et al (38) described an activation-induced CD5 ligand (CD5L) expressed by activated murine B cells, as well as T cell clones. Similarly, Bikah et al (39) have described a ligand expressed by murine peritoneal B cells, activated splenic B cells, and B lymphoma cell lines.…”