Tolerance-Inducing Passenger Leukocytes in Perinatal Skin Grafts of the Mouse

Abstract

Neonatal skin grafts have the capacity to outlive adult skin grafts, especially in situations involving H-2 antigen compatibility of donor and host. Neonatal grafts can induce a state of tolerance in their hosts; in many cases, recipients exposed to neonatal allografts fail to reject adult grafts from the same donor strain. In the H-2 antigen compatible C3H ↔ CBA combination, survival of neonatal skin grafts is correlated with the emigration of passenger leukocytes from the graft vasculature. Removal of a neonatal C3H skin graft has no effect on the unresponsive state of the host with respect to subsequent grafts of adult tissue. Donor leukocytes arc present in various tissues of the tolerant CBA host, and treatments (such as irradiation) that eliminate the normal leukocytic population of a neonatal C3H skin graft also eliminate the likelihood of skin graft survival and block the establishment of tolerance. In the C57BL/6 (B6) male-to-female system, survival of neonatal skin grafts is not correlated with emigration of passenger cells. Removal of a neonatal male B6 graft breaks the tolerance of the female host. The tolerant female is not a leukocyte chimera, and irradiation of the neonatal graft or replacement of the passenger cells with adult male cells does not eliminate the likelihood of graft survival nor does it block the establishment of tolerance. Moreover, passenger cells play no part in tolerance to Sk antigen incompatible grafts; Sk (skin-specific) antigens do not occur in lymphocytes. The anomalous survival of neonatal skin rafts, evidently promoted by different mechanisms in different donor-host combinations, remains to be clarified. And it remains also to be determined whether the idiosyncratic performance of certain neonatal passenger cells has any physiological relevance.