title: Failure of anti-Forssman antibodies to induce rejection of mouse heart xenografts.
abstract: The Forssman antigen has been proposed to be a target for the xenograft reaction in selected species combinations, including the rat and mouse, which are Forssman-negative and -positive species respectively. The mouse represents an important experimental model for a variety of immune-mediated disease processes, and the availability of a simple, inexpensive target antigen could provide an important tool for studying a selected portion of the immunologic basis for the rejection of xenografts. We have examined the potential that antibodies directed against mouse Forssman antigen could cause the hyperacute rejection of mouse heart xenografts in naive rat recipients. The Forssman antibodies tested included rat anti-mouse (R-anti-M) antiserum, R-anti-M antiserum depleted of anti-Forssman (anti-F) antibodies, rat anti-sheep red blood cell (SRBC) antiserum containing anti-F antibodies and a rat monoclonal anti-F IgM antibody. Our results demonstrate that the R-anti-M antiserum at day 4 post transplantation displayed significant titers (1:512-4096) of hemagglutinating antibodies for SRBC and mild to moderate levels of IgM that specifically binds to Forssman glycolipid (GalNAcalpha1-3GalNAcbeta1-3Galalpha1-4Galbeta1- 4Glcbeta1-1ceramide) as measured by an enzyme-linked immunosorbent assay (ELISA). Passive transfer of the R-anti-M serum to rats receiving mouse cardiac grafts immediately after transplantation caused hyperacute rejection of the xenografts. Sequential immunoabsorption of R-anti-M sera with SRBCs resulted in total removal of the anti-Forssman activity (as defined by negative hemagglutination titer and minimal binding to Forssman glycolipid in ELISA). The anti-F Ab-depleted R-anti-M antisera, however, retained the capacity to induce hyperacute rejection of the mouse hearts [n = 6, median survival time (MST) 13 min] when passively transferred to rat recipients. Anti-Forssman antibodies induced by immunization of LEW rats with SRBCs or a rat anti-Forssman monoclonal antibody, mAb M.1.22.25, exhibited substantial anti-Forssman activity (hemagglutinating titer 1:512-4096 and moderate-to-strong binding to Forssman glycolipid in ELISA respectively). These antibodies also failed, however, to trigger hyperacute rejection of mouse cardiac xenografts. In conclusion, our results suggest that the rat anti-Forssman antibodies, including those stimulated by mouse cardiac xenografts, do not appear to play a role in the immediate (hyperacute) rejection of mouse heart xenografts.
authors.affiliation: Department of Cardiothoracic Surgery School of Medicine, University of Southern California, Los Angeles 90033, USA.
authors.forename: G D
authors.initials: GD
authors.lastname: Wu
authors.forename: G
authors.initials: G
authors.lastname: Fujii
authors.forename: E
authors.initials: E
authors.lastname: Johnson
authors.forename: J
authors.initials: J
authors.lastname: Swensson
authors.forename: O
authors.initials: O
authors.lastname: Oakley
authors.forename: D V
authors.initials: DV
authors.lastname: Cramer
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D005577:Forssman Antigen / Q000276:immunology*; D006084:Graft Rejection / Q000276:immunology*; D016027:Heart Transplantation; D051379:Mice; D051381:Rats; D014181:Transplantation Immunology; D014183:Transplantation, Heterologous
chemical_list: D000906:Antibodies; D005577:Forssman Antigen