HLA-mismatched renal transplantation without maintenance immunosuppression.
Five patients with end-stage renal disease received combined bone marrow and kidney transplants from HLA single-haplotype mismatched living related donors, with the use of a nonmyeloablative preparative regimen. Transient chimerism and reversible capillary leak syndrome developed in all recipients. Irreversible humoral rejection occurred in one patient. In the other four recipients, it was possible to discontinue all immunosuppressive therapy 9 to 14 months after the transplantation, and renal function has remained stable for 2.0 to 5.3 years since transplantation. The T cells from these four recipients, tested in vitro, showed donor-specific unresponsiveness and in specimens from allograft biopsies, obtained after withdrawal of immunosuppressive therapy, there were high levels of P3 (FOXP3) messenger RNA (mRNA) but not granzyme B mRNA.
Kawai
Tatsuo
T
Transplantation Unit, Massachusetts General Hospital, and Harvard Medical School, Boston, USA.
Cosimi
A Benedict
AB
Spitzer
Thomas R
TR
Tolkoff-Rubin
Nina
N
Suthanthiran
Manikkam
M
Saidman
Susan L
SL
Shaffer
Juanita
J
Preffer
Frederic I
FI
Ding
Ruchuang
R
Sharma
Vijay
V
Fishman
Jay A
JA
Dey
Bimalangshu
B
Ko
Dicken S C
DS
Hertl
Martin
M
Goes
Nelson B
NB
Wong
Waichi
W
Williams
Winfred W
WW
Colvin
Robert B
RB
Sykes
Megan
M
Sachs
David H
DH
D000328:Adult; D001706:Biopsy; D016026:Bone Marrow Transplantation; D003131:Combined Modality Therapy; D005260:Female; D006084:Graft Rejection / Q000276:immunology; D053804:Granzymes / Q000235:genetics / Q000378:metabolism; D051541:Hepatocyte Nuclear Factor 3-alpha / Q000235:genetics / Q000378:metabolism; D006650:Histocompatibility Testing; D006801:Humans; D007165:Immunosuppression Therapy; D007668:Kidney / Q000033:anatomy & histology / Q000648:ultrastructure; D007676:Kidney Failure, Chronic / Q000601:surgery*; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000302:isolation & purification / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D018183:Transplantation Chimera / Q000276:immunology*; D019172:Transplantation Conditioning; D014181:Transplantation Immunology; D023001:Transplantation Tolerance / Q000276:immunology*; D014184:Transplantation, Homologous / Q000276:immunology
C496499:FOXA1 protein, human; D051541:Hepatocyte Nuclear Factor 3-alpha; D012333:RNA, Messenger; D053804:Granzymes