Postoperative administration of donor B cells induces rat kidney allograft acceptance: lack of association with Th2 cytokine expression in long-term accepted grafts.
BACKGROUND
Although donor leukocytes are only thought to prolong survival when administered before transplantation, recent evidence shows that they are effective at transplantation. This study aims to identify the leukocyte subset that is most active in prolonging kidney allograft survival and examine the cytokine expression in long-term acceptance.


METHODS
PVG rat kidneys were transplanted to completely MHC class I and class II-mismatched DA recipients. Donor B cells or T cells, purified by negative selection, were injected i.v. at the time of transplantation. Expression of interleukin (IL)-2, IL-4, IL-10, interferon (IFN)-gamma, and transforming growth factor-beta mRNA was measured by quantitative real-time polymerase chain reaction (PCR). Immunohistochemical analysis and terminal deoxynucleotide transferase-mediated dUTP nick-end labelling (TUNEL) staining was used to identify infiltrating cells and apoptotic cells, respectively, in sections of kidney allografts.


RESULTS
Median kidney graft survival time (MST) of B cell-treated animals (n=5) was >300 days, compared with 7 days in untreated animals (n=7) (P=0.003), whereas animals treated with the same number of T cells (n=6) had a MST of 17 days (P=0.1 vs. untreated, P=0.03 vs. B cell-treated). Examination of the long-term (>300 days) accepted grafts from B cell-treated recipients showed little evidence of kidney damage but a moderate perivascular infiltrate consisting of T and B cells. This infiltrate seemed to be quiescent because there was no detectable expression of IL-2 receptors or of apoptotic cells. It produced little or no cytokine mRNA, because expression in the long-term accepted grafts was similar to levels in normal kidneys or syngeneic transplants. There was a marked increase of cytokine mRNA early after transplantation in both leukocyte-treated and untreated grafts, with more rapid appearance of IFN-gamma and IL-10 in leukocyte-treated grafts.


CONCLUSIONS
Donor B cells efficiently induce long-term acceptance of transplanted kidneys in a fully MHC-mismatched rat model when administered at transplantation, by a mechanism that seems to be independent of Th2 cytokine expression within the long-term accepted graft.
Yan
Yiqun
Y
AW Morrow Liver Immunobiology Laboratory, Centenary Institute, and Department of Pathology, Royal Prince Alfred Hospital, New South Wales 2050, Australia..
van der Putten
Karien
K
Bowen
David G
DG
Painter
Dorothy M
DM
Kohar
Jimmy
J
Sharland
Alexandra F
AF
McCaughan
Geoffrey W
GW
Bishop
G Alex
GA
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D006084:Graft Rejection; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000401:mortality; D016753:Interleukin-10 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D007668:Kidney / Q000473:pathology; D016030:Kidney Transplantation / Q000401:mortality; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D018418:Th2 Cells / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D014184:Transplantation, Homologous
D016207:Cytokines; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D015847:Interleukin-4