Limits...
Role of the thymus in transplantation tolerance in miniature swine. I. Requirement of the thymus for rapid and stable induction of tolerance to class I-mismatched renal allografts.

Yamada K, Gianello PR, Ierino FL, Lorf T, Shimizu A, Meehan S, Colvin RB, Sachs DH - J. Exp. Med. (1997)

Bottom Line: Thymectomized swine developed acute cellular rejection characterized by a T cell (CD25(+)) infiltrate, tubulitis, endothelialitis and glomerulitis, and anti-donor CTL reactivity in vitro.Nonthymectomized and sham thymectomized animals had a mild T cell infiltrate with few CD25(+) cells and no anti-donor CTL response in vitro.These results indicate that the thymus is required for rapid and stable induction of tolerance.

View Article: PubMed Central - PubMed

Affiliation: Transplantation Biology Research Center, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, 02129, USA.

ABSTRACT
The almost uniform failure in transplant patients of tolerance-inducing regimens that have been found to be effective in rodents, has made it necessary to examine large animal models before testing of new approaches clinically. Miniature swine have been shown to share many relevant immunologic parameters with humans, and because of their reproducible genetics, have proved extremely useful in providing such a large animal model. We have previously shown that indefinite systemic tolerance to renal allografts in miniature swine is induced in 100% of cases across a two-haplotype class I plus minor histocompatibility antigen disparity by a 12-d course of Cyclosporine A (CyA), in contrast to irreversible rejection observed uniformly without CyA treatment. In the present study, we have examined the role of the thymus during the induction of tolerance by performing a complete thymectomy 21 d before renal transplantation. This analysis demonstrated a striking difference between thymectomized and nonthymectomized animals. Thymectomized swine developed acute cellular rejection characterized by a T cell (CD25(+)) infiltrate, tubulitis, endothelialitis and glomerulitis, and anti-donor CTL reactivity in vitro. Nonthymectomized and sham thymectomized animals had a mild T cell infiltrate with few CD25(+) cells and no anti-donor CTL response in vitro. These results indicate that the thymus is required for rapid and stable induction of tolerance.

Show MeSH

Related in: MedlinePlus

Macroscopic findings of a completely resected thymus from a  thymectomized animal.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2199031&req=5

Figure 2: Macroscopic findings of a completely resected thymus from a thymectomized animal.

Mentions: The surgical procedures used for kidney transplants have been described in detail previously (24, 25). A semipermanent indwelling Hickman silastic central venous catheter was placed surgically into the external jugular vein. The catheter facilitated CyA administration and frequent blood sampling for monitoring of renal function, whole blood CyA levels, and in vitro assays. A complete thymectomy was carried out 21 d before kidney transplantation in the thymectomized group. The pretracheal muscles were retracted exposing the trachea from the cervico-thoracic junction to the mandibular area, as well as the thymus. The cervical portion of the thymus was then dissected and excised. To achieve a complete thymectomy, a partial sternotomy was then performed, and the thoracic portion of the thymus was exposed. In the chest, the thymus consisted of nonencapsulated tissue adherent to the pericardium, the pleura, and the large vessels, and therefore careful dissection of this portion of the thymus was required to complete the thymectomy (Fig. 2). Removed thymic tissue was examined histologically and showed active thymopoiesis (data not shown). Sham thymectomy was performed in an identical fashion to complete thymectomy; however, thymic tissue was not removed.


Role of the thymus in transplantation tolerance in miniature swine. I. Requirement of the thymus for rapid and stable induction of tolerance to class I-mismatched renal allografts.

Yamada K, Gianello PR, Ierino FL, Lorf T, Shimizu A, Meehan S, Colvin RB, Sachs DH - J. Exp. Med. (1997)

Macroscopic findings of a completely resected thymus from a  thymectomized animal.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2199031&req=5

Figure 2: Macroscopic findings of a completely resected thymus from a thymectomized animal.
Mentions: The surgical procedures used for kidney transplants have been described in detail previously (24, 25). A semipermanent indwelling Hickman silastic central venous catheter was placed surgically into the external jugular vein. The catheter facilitated CyA administration and frequent blood sampling for monitoring of renal function, whole blood CyA levels, and in vitro assays. A complete thymectomy was carried out 21 d before kidney transplantation in the thymectomized group. The pretracheal muscles were retracted exposing the trachea from the cervico-thoracic junction to the mandibular area, as well as the thymus. The cervical portion of the thymus was then dissected and excised. To achieve a complete thymectomy, a partial sternotomy was then performed, and the thoracic portion of the thymus was exposed. In the chest, the thymus consisted of nonencapsulated tissue adherent to the pericardium, the pleura, and the large vessels, and therefore careful dissection of this portion of the thymus was required to complete the thymectomy (Fig. 2). Removed thymic tissue was examined histologically and showed active thymopoiesis (data not shown). Sham thymectomy was performed in an identical fashion to complete thymectomy; however, thymic tissue was not removed.

Bottom Line: Thymectomized swine developed acute cellular rejection characterized by a T cell (CD25(+)) infiltrate, tubulitis, endothelialitis and glomerulitis, and anti-donor CTL reactivity in vitro.Nonthymectomized and sham thymectomized animals had a mild T cell infiltrate with few CD25(+) cells and no anti-donor CTL response in vitro.These results indicate that the thymus is required for rapid and stable induction of tolerance.

View Article: PubMed Central - PubMed

Affiliation: Transplantation Biology Research Center, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, 02129, USA.

ABSTRACT
The almost uniform failure in transplant patients of tolerance-inducing regimens that have been found to be effective in rodents, has made it necessary to examine large animal models before testing of new approaches clinically. Miniature swine have been shown to share many relevant immunologic parameters with humans, and because of their reproducible genetics, have proved extremely useful in providing such a large animal model. We have previously shown that indefinite systemic tolerance to renal allografts in miniature swine is induced in 100% of cases across a two-haplotype class I plus minor histocompatibility antigen disparity by a 12-d course of Cyclosporine A (CyA), in contrast to irreversible rejection observed uniformly without CyA treatment. In the present study, we have examined the role of the thymus during the induction of tolerance by performing a complete thymectomy 21 d before renal transplantation. This analysis demonstrated a striking difference between thymectomized and nonthymectomized animals. Thymectomized swine developed acute cellular rejection characterized by a T cell (CD25(+)) infiltrate, tubulitis, endothelialitis and glomerulitis, and anti-donor CTL reactivity in vitro. Nonthymectomized and sham thymectomized animals had a mild T cell infiltrate with few CD25(+) cells and no anti-donor CTL response in vitro. These results indicate that the thymus is required for rapid and stable induction of tolerance.

Show MeSH
Related in: MedlinePlus