Generation of NK1.1+ T cell antigen receptor alpha/beta+ thymocytes associated with intact thymic structure - PubMed (original) (raw)

Comparative Study

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

K Nakagawa et al. Proc Natl Acad Sci U S A. 1997.

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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.

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Figures

Figure 1

Figure 1

Proportion of NK1.1+ TCR-α/β+ cells in lymphoid tissues from aly/aly, aly/+ and B6 mice. Representative FACS profiles of NK1.1+ TCR-α/β+ (average ± SD) cells in the thymus (A) and spleen and BM (B) from three mice are shown. The actual numbers of NK1.1+ TCR-α/β+ thymocytes are shown below A.

Figure 2

Figure 2

Proportion of NK1.1+ TCR-α/β+ thymocytes in BM chimeras. Four kinds of BM chimeras prepared by reciprocal BM transplantation between aly/aly and aly/+ mice were analyzed for the population size of NK1.1+ TCR-α/β+ thymocytes (A). (B) Data for the average ± SD (number) of three to five chimeric mice.

Figure 3

Figure 3

Proportion of NK1.1+ TCR-α/β+ thymocytes in [aly/aly → B6.PL-Thy 1.1] BM chimeras. A representative profile of NK1.1+ TCR-α/β+ cells in whole thymocytes is shown from two separate experiments (Left). The origin of thymocytes was determined by anti-Thy 1 mAb (Right).

Figure 4

Figure 4

Histopathology of the thymus from aly/aly and aly/+ and chimeric mice. Thymic sections obtained from aly/+ (A, C,and E), aly/aly (B, D, and F), [aly/alyaly/+] (G), and [aly/+ → aly/_aly_] (H) mice were stained either with hematoxylin/eosin (HE) (A, B, G, and H), ER-TR4 (C and D) or ER-TR5 (E and F). [HE staining (A, B, G, and H) = ×40; immunohistochemical staining (C, D, E, and F) = ×400.]

Figure 5

Figure 5

Proportion of NK1.1+ TCR-α/β+ cells in grafted thymi. Adult thymectomized aly/aly mice were reconstituted with aly/aly BM cells followed by grafting of (B6 × B10.G)F1 fetal thymi, and the proportion of the NK1.1+ TCR-α/β+ cells in the thymi was analyzed (A). Average ± SD (%) of three chimeras was indicated at the bottom. The origin of thymocytes was determined with anti-Dq mAb (B).

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