Identification of a novel inducible cell-surface ligand of CD5 on activated lymphocytes.
CD5 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 of T cell activation and in T cell-antigen presenting cell interactions. Using a CD5-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 induce transient expression of CD5L on B lymphocytes that lasts for approximately 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 on N-glycanase completely abrogates its ability to bind activated splenocytes. It addition to splenocytes, CD5L is expressed on activated murine T cell clones. Immunoprecipitation, antibody, and recombinant protein blocking studies indicate that CD5L 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 immune responses.
Biancone
L
L
Department of Pathology Harvard Medical School and Pathology Research, Massachusetts General Hospital, Boston 02129, USA.
Bowen
M A
MA
Lim
A
A
Aruffo
A
A
Andres
G
G
Stamenkovic
I
I
D000818:Animals; D018956:CD5 Antigens / Q000032:analysis*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D015433:Glomerulonephritis, Membranous / Q000517:prevention & control; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011956:Receptors, Cell Surface / Q000032:analysis*; D013050:Spectrometry, Fluorescence; D013154:Spleen / Q000166:cytology / Q000378:metabolism
D018956:CD5 Antigens; D011956:Receptors, Cell Surface