A strategy for organ allografts without using immunosuppressants or irradiation.
A strategy to achieve regular and long lasting organ and tissue allografts without using immunosuppressants and/or irradiation has been established for mice. One hundred percent of skin allografts can be induced to survive >350 days after transplantation if spleen cells from the same donors are first injected into the portal vein of the recipients. The mechanisms underlying this long-term tolerance induction can be described as follows: (i) donor T cells from the spleen of the donor facilitate the acceptance of the allogeneic engraftment, (ii) donor-specific anergy is induced in the cytotoxic T-lymphocytes of the recipients, (iii) T helper type 2 cells become the dominant T cells in the recipients that are accepting the skin transplants, and (iv) a lasting chimerism (microchimerism) is established in these recipients. This strategy, perhaps with minor modifications, might permit one also to overcome major barriers to organ allografting in humans. If this were the case, it could represent production of long lasting immunologic tolerance without need for irradiation or cytotoxic chemo-preparative regimen and as such could greatly facilitate allotransplantation free of episodes of chronic or acute rejection or toxic and damaging preparatory regimens.
Morita
H
H
First Department of Surgery, Kansai Medical University, Moriguchi City, Osaka 570, Japan.
Sugiura
K
K
Inaba
M
M
Jin
T
T
Ishikawa
J
J
Lian
Z
Z
Adachi
Y
Y
Sogo
S
S
Yamanishi
K
K
Taki
H
H
Adachi
M
M
Noumi
T
T
Kamiyama
Y
Y
Good
R A
RA
Ikehara
S
S
D019264:Adoptive Transfer; D000818:Animals; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006085:Graft Survival / Q000276:immunology*; D007108:Immune Tolerance; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D016038:Skin Transplantation / Q000276:immunology / Q000379:methods*; D013154:Spleen / Q000276:immunology*; D014184:Transplantation, Homologous; D014916:Whole-Body Irradiation
D007166:Immunosuppressive Agents