The immunologic role of IFN-gamma in ACI to Lewis kidney transplantation.
BACKGROUND
One of the proposed mechanisms of tolerance induction is the Th-1/Th-2 paradigm. The Th-1 cell is proinflammatory, secreting IFN-gamma and IL-2. Conversely, the Th-2 cell is anti-inflammatory, secreting IL-4 and IL-10. In our earlier studies a shift toward Th-2 dominance was required for tolerance induction in this model.


METHODS
ACI and Lewis rats were used as donors and recipients, respectively. Twelve hours prior to engraftment, rapamycin 1.5 mg/kg po and cyclosporin 10 mg/kg sc were given, followed by 5 mg/kg sc postop (days 1-7). Lewis rats were used as isografts. Functional allograft tolerance was induced consistently in 100% of the recipients with 50% of the allografts exhibiting normal histology beyond 120 days. Qualitative RT-PCR was performed on the grafts to determine IFN-gamma expression with beta-actin housekeeping gene as control.


RESULTS
IFN-gamma was expressed in all untreated allografts (5/5) and all treated, yet rejecting, allografts (4/4). None of the isografts (0/5) or histologically tolerant allografts (0/4) expressed IFN-gamma. This distribution was statistically significant (P < 0.001, Fischer's exact test).


CONCLUSIONS
Our findings support a shift from Th-2 to Th-1 predominance as the corollary mechanism responsible for preventing histologic tolerance.
Naar
J D
JD
Division of Transplant Surgery, Medical College of Virginia/Virginia Commonwealth University, Richmond, Virginia, 23298-0254, USA.
Fisher
R A
RA
Saggi
B H
BH
Obias
V
V
Goggins
W C
WC
Tawes
J W
JW
Wakely
P E
PE
Posner
M P
MP
D000818:Animals; D016572:Cyclosporine / Q000494:pharmacology; D015870:Gene Expression / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology*; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D011090:Polyenes / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011917:Rats, Inbred Lew; D020123:Sirolimus; D014184:Transplantation, Homologous
D007166:Immunosuppressive Agents; D011090:Polyenes; D012333:RNA, Messenger; D007371:Interferon-gamma; D016572:Cyclosporine; D020123:Sirolimus