Infectious tolerance develops after intrathymic alloantigen-induced acceptance of rat heart allografts can be adoptively transferred.
BACKGROUND
We have shown that intrathymic (IT) injection of alloantigen with antirat lymphocyte serum (ALS) treatment can induce donor-specific allograft acceptance. The purpose of this study was to investigate whether T-regulatory (T-reg) cells play a role in the maintenance of donor-specific heart graft tolerance that develops after IT injection of Lewis (LEW, RT1(l)) alloantigen into a Dark Agouti (DA, RT1(a)).


METHODS
Naïve DA rats were injected IT with 2.5 x10(7) LEW donor splenocytes and injected intraperitoneally with 1 mL ALS. Twenty-one days after pretreatment, a LEW or Brown Norway (BN, RT1(n)) heart was transplanted into a treated DA recipient. Splenocytes (1 x 10(8) or 5 x 10(7)) from a LEW heart-tolerant long-term survivor (LTS; >60 days) DA recipient were harvested and adoptively transferred (AT) into an irradiated (450 rad) naïve DA rat 24 hours before transplanting a LEW heart.


RESULTS
All LEW heart allografts were rejected by untreated DA rats in a mean survival time (MST) of 7.4 +/- 1.7 days (n=7). In contrast, 66.7% of LEW heart grafts into IT+ALS-pretreated DA recipients were accepted indefinitely (n=24). When either 1 x 10(8) (n=5) or 5 x 10(7) (n=5) splenocytes from a LEW heart graft-tolerant LTS (>60 days) DA recipient were AT into a new naïve DA rat, all new LEW heart grafts were accepted indefinitely.


CONCLUSIONS
The donor-specific tolerance that develops after IT+ALS-induced LEW heart acceptance by DA recipients can be transferred adoptively to new naïve DA recipients, thus indicating that it is infectious tolerance.
Takayashiki
Tsukasa
T
Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA.
Asakura
Hiroyuki
H
Ku
Grace
G
Kataoka
Masaaki
M
Flye
M Wayne
MW
D019264:Adoptive Transfer; D000818:Animals; D006085:Graft Survival / Q000276:immunology; D016027:Heart Transplantation / Q000276:immunology*; D007106:Immune Sera; D007108:Immune Tolerance / Q000276:immunology*; D016130:Immunophenotyping; D007165:Immunosuppression Therapy / Q000379:methods; D007519:Isoantigens / Q000276:immunology*; D008297:Male; D009206:Myocardium / Q000276:immunology / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew; D013045:Species Specificity; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology*
D007106:Immune Sera; D007519:Isoantigens