Control of Self Reactive CTL Independent of Thymic Selection

Abstract

Normal mice are extemely resistant to experimentally introduced CTL reactive against self MHC: B-reactive CTL could not be recovered from (A X B)F₁ mice injected i.p. with 2 × 10⁸ strain A spleen cells, whereas third party reactive CTL of donor origin were found. Irradiation (600 rad) of F₁ mice before injection abolished this resistance, and B reactive CTL could be readily recovered. In nude mice of strain A, which carried a grafted thymus of strain B and are therefore tolerant of B by thymic negative selection, B-reactive CTL were recovered after injection of as few as 10⁷ normal strain A spleen cells.

Thus self-class I reactive CTL are vigorously eliminated in normal mice. This mechanism is dependent on radiosensitive, antigen expressing peripheral cells, presumably of bone marrow origin.

The vigorous elimination of self class I reactive CTL is in contrast to the fate of self class II reactive T helper cells: A → (A x B)F₁ injections can lead to T helper mediated “lymphoproliferative”, but usually nonlethal GVH. The lethality in this situation may be avoided by the buffer system described above. Whether the buffer system is required to maintain normal self tolerance is not known.