Infectious tolerance mediated by CD8+ T-suppresor cells after UV-B-irradiated donor-specific transfusion and rat heart transplantation.
OBJECTIVE
CD8+CD28- human T-suppressor cells (Ts), which can be generated in vitro, act directly on APC rendering them tolerogenic to unprimed and primed CD4+ T cells. The aim of this study was to investigate the possibility that CD8+ T cells mediate the induction of tolerance in a heart transplantation model in rodents.


METHODS
Blood from Lewis rats was UV-B-irradiated and transfused into ACI recipients on days -21, -14, and -7 before heart allograft transplantation on day 0. CD4(+) and CD8(+) T cells were positively selected from ACI rats, which had tolerated Lewis heart allografts for more than 100 days and were adoptively transferred to naive ACI rats pretreated (day -1) with gamma irradiation. These ACI rats underwent transplantation with Lewis hearts 24 hours after adoptive transfer of putative T-suppressor cells.


RESULTS
Adoptive transfer of CD8(+) T cells from tolerant ACI to naive ACI rats significantly prolonged Lewis heart mean allograft survival time (MST +/- SD) to 69 +/- 13 days as compared with 15 +/- 1 and 14 +/- 1 days in animals adoptively transferred with CD4+ T cells or untreated controls, respectively (P < .001). Similarly, adoptive transfer of CD8(+) T cells from secondary ACI recipients to naive syngeneic animals also significantly prolonged survival of heart allografts to MST +/- SD of 72 +/- 4 for CD8(+) and 15 +/- 4 days for CD4(+) T cells (P < .001).


CONCLUSIONS
These data demonstrate that allogeneic tolerance induced in ACI recipients by treatment with UV-B-irradiated blood from Lewis donors is mediated by CD8+ T-suppressor cells.
Witkowski
P
P
Department of Surgery, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA. pw2004@columbia.edu
Liu
J W
JW
Jin
M X
MX
Liu
Z
Z
Suciu-Foca
N
N
Hardy
M A
MA
D019264:Adoptive Transfer; D000818:Animals; D001803:Blood Transfusion; D006085:Graft Survival / Q000528:radiation effects*; D016027:Heart Transplantation / Q000276:immunology*; D017710:Lymphocyte Transfusion; D051381:Rats; D011912:Rats, Inbred ACI; D011917:Rats, Inbred Lew; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000528:radiation effects*; D013997:Time Factors; D023001:Transplantation Tolerance / Q000276:immunology*; D014184:Transplantation, Homologous / Q000276:immunology; D014466:Ultraviolet Rays