Role of CD41CD251 regulatory T cells from naive host thymus in the induction of acquired transplant tolerance by immunization with allo-major histocompatibility complex peptide.
BACKGROUND
Immunization with allo-major histocompatibility complex peptide induces operational tolerance, whereas thymectomy abrogates this effect. We hypothesized that recent thymic emigrants with regulatory function are important in the induction of acquired transplant tolerance in this system.


METHODS
In this study, we examined the possibility of restoring transplant tolerance to thymectomized (TMX) ACI recipients with concomitant adoptive transfer of syngeneic T cells indirectly primed with a single immunodominant Wistar Furth allo-major histocompatibility complex class I peptide (peptide 5, residues 93-109) and unmodified thymocytes or CD4+CD25+ thymic T cells.


RESULTS
Co-transfer of in vivo allopeptide-primed T cells and naive syngeneic thymic T cells on day -7 restored permanent acceptance of cardiac allografts to 70% of transiently antilymphocyte serum-immunosuppressed TMX recipients. Similarly, the adoptive transfer of allopeptide-primed T cells led to 100% donor-specific permanent graft acceptance among transiently antilymphocyte serum-immunosuppressed TMX recipients with renal subcapsular syngeneic thymic grafts. To demonstrate the role of regulatory T cells among new thymic emigrants in the induction of tolerance, we showed that the co-transfer of CD4+CD25+ but not CD4+CD25- thymic T cells with allopeptide-primed syngeneic T cells restored tolerance to TMX recipients. It seems that the induction of transplant tolerance in this system is dependent on the presence of CD4+CD25+ regulatory T cells among the recent thymic emigrants.


CONCLUSIONS
This study suggests that CD4+CD25+ regulatory T cells specific for the induction of transplant tolerance are similar in origin, phenotype, and function to those involved in the maintenance of self-tolerance and the prevention of autoimmunity.
Oluwole
Olakunle O
OO
Department of Surgery, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
DePaz
Hector A
HA
Adeyeri
Ayotunde
A
Jin
Ming-Xing
MX
Hardy
Mark A
MA
Oluwole
Soji F
SF
D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D017690:Cell Transplantation; D016027:Heart Transplantation / Q000276:immunology*; D006649:Histocompatibility Antigens / Q000276:immunology*; D007519:Isoantigens / Q000276:immunology; D007668:Kidney / Q000601:surgery; D010446:Peptide Fragments / Q000276:immunology; D051381:Rats; D011919:Rats, Inbred Strains; D015375:Receptors, Interleukin-2 / Q000378:metabolism*; D013934:Thymectomy; D013950:Thymus Gland / Q000166:cytology; D023001:Transplantation Tolerance / Q000502:physiology*; D016042:Transplantation, Heterotopic; D014185:Transplantation, Isogeneic
D006649:Histocompatibility Antigens; D007519:Isoantigens; D010446:Peptide Fragments; D015375:Receptors, Interleukin-2