Immunomodulation by intrathymic injection of donor leukocytes in rhesus monkeys.

BACKGROUND

Several studies have demonstrated that intrathymic injection of donor cells into adult rodents can result in long-term allograft survival. The rationale for using the intrathymic route of donor cell administration is that in the thymic environment immature T cells are educated to discriminate between self and non-self antigens. The validity of this approach was tested in non-human primates.

METHODS

The effect of the intrathymic injection of allogeneic donor cells was investigated in rhesus monkeys and compared with IV and intracutaneous administration of donor cells. Intrathymic injections were carried out without and with antithymocyte globulin. All animals received subsequently an allogeneic skin graft of the same donor and no immunosuppression post transplantation.

RESULTS

Skin graft survival was slightly shorter in animals treated with IC donor cell injections (mean survival time [MST]=8.9+/-0.52) than untreated control animals (MST=10.0+/-0.44), indicating that this route caused sensitisation. Intravenous donor cell injection showed prolongation of graft survival times (MST=11.6+/-1.69). Intrathymic donor cell injection resulted in a graft survival of 9.2+/-1.44 days although addition of antithymocyte globulin slightly prolonged graft survival to 10.3+/-2.84 (not significant). Whereas the cellular responses after intrathymic and intravenous donor cell injections increased, antithymocyte globulin treated animals did not show an increased cellular response. Recipients of intrathymic donor cells showed a significantly decreased humoral anti-donor response as compared to other groups.

CONCLUSIONS

Donor cell pretreatment alters the subsequent response to an allogeneic skin graft in monkeys and is dependent on the route of donor cell administration. This is also reflected in the alloantibody response and the in vitro cellular reactivity. Intrathymic administration of donor cells does not lead to prolonged skin graft acceptance.