The pig-to-primate immune response: relevance for xenotransplantation.
BACKGROUND
The allotransplantation of some solid organs can be associated with a graft-vs.-host (GVH) response from the activity of donor B or T cells. We have investigated whether there is a risk of a GVH response following pig-to-primate organ xenotransplantation.


METHODS
The responses of 16 pigs (six farm-housed wild-type and five wild-type housed under high herd health conditions [all designated WT], and 5 alpha1,3-galactosyltransferase gene-knockout [GT-KO] housed under high herd health conditions) to human (n = 6) and baboon (n = 6) peripheral blood mononuclear cells (PBMC) were determined. Assays included flow cytometry, complement-dependent cytotoxicity, and mixed lymphocyte reaction.


RESULTS
Anti-primate cytotoxic IgM antibodies were detected in the sera of all pigs, but anti-primate IgG antibodies were minimal. All pigs demonstrated a cellular proliferative response to primate PBMC that was equivalent to, or greater than, the allo response. The strength of the pig-to-primate GVH responses was proportional to the health status of the pigs, those from a high health status herd, particularly from a specific pathogen-free herd maintained under clean husbandry conditions, where colonization of the gastrointestinal tract may be reduced, having lower responses.


CONCLUSIONS
After pig organ transplantation in a primate, if the organ is from an early-weaned, early-segregated GT-KO pig, the strength of a GVH response is likely to be relatively weak. Although not investigated here, any GVH response is likely to be suppressed by the immunosuppressive therapy administered to the recipient to suppress the anti-donor immune response.
Tai
Hao-Chih
HC
Department of Surgery, The Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA 15261, USA.
Zhu
Xiaocheng
X
Hara
Hidetaka
H
Lin
Yih Jyh
YJ
Ezzelarab
Mohamed
M
Long
Cassandra
C
Ball
Suyapa
S
Ayares
David
D
Cooper
David K C
DK
D000818:Animals; D030801:Animals, Genetically Modified / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic; D005700:Galactosyltransferases / Q000235:genetics; D006086:Graft vs Host Disease / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D048530:Papio anubis / Q000276:immunology*; D013552:Swine / Q000235:genetics* / Q000276:immunology*; D014183:Transplantation, Heterologous / Q000276:immunology*
D007074:Immunoglobulin G; D005700:Galactosyltransferases; C047006:N-acetyllactosaminide alpha-1,3-galactosyltransferase