Recombinant dimeric MHC antigens protect cardiac allografts from rejection and visualize alloreactive T cells.
Monomeric and dimeric soluble major histocompatibility complex (MHC) molecules down-regulate activated T cells in an antigen-specific manner in vitro. This property could be exploited to modulate alloresponses in vivo but has remained difficult to demonstrate. Here, intraperitoneal infusion of a Lewis-derived rat MHC class I molecule, RT1.A(l)-Fc, in Dark Agouti (RT1.A(a)) recipient rats prolonged cardiac graft survival, which led to permanent engraftment. This effect was mediated by T cell impairment of target cell lysis by CD8+ T cells and down-regulation of interferon-gamma production by CD4+ T cells. The binding of the dimeric MHC allowed ex vivo visualization of alloreactive T cells in peripheral blood, splenocytes, and allografts, revealing low frequency of alloreactive CD8+ T cells after establishment of permanent engraftment of cardiac allografts. Thus, these data show the potential of dimeric MHC molecules to promote graft survival and allow visualization of alloreactive T cells.
Fried
Ari
A
C51-F, Department of Internal Medicine, 200 Hawkins Dr., Iowa City, IA 52242, USA.
Berg
Martina
M
Sharma
Bhavna
B
Bonde
Sabrina
S
Zavazava
Nicholas
N
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D019281:Dimerization; D004195:Disease Models, Animal; D006084:Graft Rejection / Q000276:immunology*; D006085:Graft Survival / Q000187:drug effects / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology*; D006649:Histocompatibility Antigens / Q000008:administration & dosage* / Q000276:immunology; D007141:Immunoglobulin Fc Fragments / Q000008:administration & dosage* / Q000276:immunology; D066298:In Vitro Techniques; D007263:Infusions, Parenteral; D008213:Lymphocyte Activation / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000276:immunology; D012995:Solubility; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D006649:Histocompatibility Antigens; D007141:Immunoglobulin Fc Fragments; D011993:Recombinant Fusion Proteins; C038353:histocompatibility antigens RT, rat