Generation of NK1.1⁺T cell antigen receptor α/β⁺thymocytes associated with intact thymic structure

Abstract

The development of T cells within the thymus is largely dependent on intact cortical and medullary epithelial cells. However, it has been reported that positive selection of natural killer antigen 1.1+ (NK1.1+) T cell antigen receptor (TCR)-alpha/beta+ thymocytes recently identified among CD4+8- and CD4-8- subpopulations is attributable to major histocompatibility complex class Ib ligands expressed on bone marrow (BM)-derived components in the thymus. In the present study, we investigated generation of NK1.1+ TCR-alpha/beta+ cells in the thymus of the aly/aly mouse which lacks lymph nodes and Peyer's patches and shows abnormalities of thymic and splenic structure. We found that the proportion of the NK1.1+ TCR-alpha/beta+ thymocytes was extremely low in these mice as compared with aly/+ and normal C57BL/6 mice. Thymic reconstitution by BM cells from aly/+ mice that possess a normal population of NK1.1+ TCR-alpha/beta+ cell population did not restore the NK1.1+ TCR-alpha/beta+ cell population in the thymus of lethally irradiated aly/aly mouse. When deoxyguanosine-treated fetal thymi from (B6 x B10.G)F1 mice were transplanted to aly/aly mice that had been thymectomized and reconstituted with BM cells of aly/aly mice, normal proportions of the NK1.1+ TCR-alpha/beta+ thymocytes were present in the thymus grafts. These findings demonstrate that the development of NK1.1+ TCR-alpha/beta+ thymocytes is accomplished under the influence not only of BM-derived components, but also of irradiation-resistant or deoxyguanosine-resistant components and an intact microenvironment of the thymus.