Autoimmune responses against renal tissue proteins in long-term surviving allograft recipients.
Major histocompatibility complex antigens (MHC) are classical targets of recipient responses to allotransplants. However, the role of an immune response directed against autologous graft tissue determinants is poorly defined. In this study, we investigated (i) whether autologous kidney tissue extract can induce an immune response to autologous kidney proteins in normal rats, and (ii) if a similar autologous response develops in the long-term surviving LEW.1A recipients of an MHC-mismatched LEW.1W kidney (RT1(u) to RT1(a)). LEW.1A rats immunized with allo- or syngeneic soluble kidney extracts developed a T-cell response to self antigens as shown by the frequency of specific IFN-gamma-producing T cells from LEW.1A rats in the presence of extracts (ELISPOT). In contrast, they responded only marginally to dominant RT1(u) determinants. The ELISPOT against fractions of soluble autologous kidney extracts separated by an FPLC gel-filtration system indicated a preferential response to megalin, a high molecular weight protein that has been shown to be involved in experimental Heymann nephritis. In a model of long-term kidney allograft survival by anti-CD28 administration, recipients also developed humoral but not cellular responses to megalin. Our data suggest that autoimmune processes develop in long-term surviving kidney allograft recipients.
Fang
Cheng
C
Institut National de la Santé Et de la Recherche Médicale (INSERM) - Université de Nantes, UMR 643, Nantes, France.
Ballet
Caroline
C
Dugast
Anne-Sophie
AS
Godard
Anne
A
Moreau
Anne
A
Usal
Claire
C
Smit
Helga
H
Vanhove
Bernard
B
Brouard
Sophie
S
Harb
Jean
J
Soulillou
Jean P
JP
D000818:Animals; D020296:Animals, Congenic; D001323:Autoantibodies / Q000096:biosynthesis / Q000097:blood*; D015551:Autoimmunity; D018106:CD28 Antigens / Q000276:immunology; D006649:Histocompatibility Antigens / Q000276:immunology*; D007114:Immunization; D007074:Immunoglobulin G / Q000032:analysis; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics; D007668:Kidney / Q000276:immunology*; D016030:Kidney Transplantation / Q000276:immunology*; D026561:Low Density Lipoprotein Receptor-Related Protein-2 / Q000276:immunology*; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011917:Rats, Inbred Lew; D013154:Spleen / Q000378:metabolism; D014020:Tissue Extracts / Q000276:immunology; D014184:Transplantation, Homologous / Q000276:immunology*
D001323:Autoantibodies; D018106:CD28 Antigens; D006649:Histocompatibility Antigens; D007074:Immunoglobulin G; D026561:Low Density Lipoprotein Receptor-Related Protein-2; D012333:RNA, Messenger; D014020:Tissue Extracts; C038353:histocompatibility antigens RT, rat; D016753:Interleukin-10; D007371:Interferon-gamma