NADPH Diaphorase-positive Dendritic Profiles in Rat Thymus Are Discrete from Autofluorescent Cells, Immunoreactive for Inducible Nitric Oxide Synthase, and Show Strain-specific Abundance Differences

Overview

Journal Immunology

Specialty Allergy & Immunology

Date 1998 Oct 10

PMID 9767470

Authors

J E DOWNING

L Virag

I W Jones

Affiliations

Soon will be listed here.

Abstract

Predisposition to autoimmune disorder in Lewis rats has been associated with abnormal hypothalamic regulation of circulating steroids, leading to inadequate suppression of T helper 1 (Th1) cell-mediated inflammatory reactions. In addition, autoimmune syndromes can be triggered within formerly resistant animals, following damage to the negative selection process of the thymus. A contribution to the autoimmune-susceptible phenotype may therefore derive from the status of thymic tolerance. One mechanism of intrathymic negative selection may involve nitric oxide. Because inducible nitric oxide synthase (iNOS) is known to be inhibitable by steroids, its expression might be different within strains having neuroendocrine disturbance. We report on a study to compare intrathymic iNOS expression in autoimmune-prone Lewis rats with other resistant strains. Interdigitating cells (IDC), darkly stained for diaphorase, were confirmed as immunoreactive for iNOS. They were located towards the medullary side of an accumulation of unstained, but autofluorescent cells (presumed to be macrophages) that circumscribes the corticomedullary zone. The role of iNOS+ IDC in the apoptotic deletion of T cells has been suggested by other studies. Despite the blunted steroidal condition reported for Lewis, nitrergic cell abundance was shown, by quantitative analysis of histochemical stain, to be on average approximately twofold lower compared with resistant strains (Fischer and Sprague-Dawley). This trend was evident in males and females, and confirmed by independent observers. We hypothesize that an intrathymic, iNOS-dependent mechanism may be important for the suppression of potentially autoreactive T-cell clones.

References

Rook G, Hernandez-Pando R, Lightman S . Hormones, peripherally activated prohormones and regulation of the Th1/Th2 balance. Immunol Today. 1994; 15(7):301-3. DOI: 10.1016/0167-5699(94)90075-2. View

Morris Jr S, Billiar T . New insights into the regulation of inducible nitric oxide synthesis. Am J Physiol. 1994; 266(6 Pt 1):E829-39. DOI: 10.1152/ajpendo.1994.266.6.E829. View

DOWNING J . Multiple nitric oxide synthase systems in adult rat thymus revealed using NADPH diaphorase histochemistry. Immunology. 1994; 82(4):659-64. PMC: 1414902. View

Wei X, Charles I, Smith A, Ure J, Feng G, Huang F . Altered immune responses in mice lacking inducible nitric oxide synthase. Nature. 1995; 375(6530):408-11. DOI: 10.1038/375408a0. View

Kendall M, Atkinson B, Munoz F, Riva C, Clarke A, von Gaudecker B . The noradrenergic innervation of the rat thymus during pregnancy and in the post partum period. J Anat. 1994; 185 ( Pt 3):617-25. PMC: 1166668. View

Fehsel K, Kroncke K, Meyer K, HUBER H, Wahn V, Kolb-Bachofen V . Nitric oxide induces apoptosis in mouse thymocytes. J Immunol. 1995; 155(6):2858-65. View

George A, Ritter M . Thymic involution with ageing: obsolescence or good housekeeping?. Immunol Today. 1996; 17(6):267-72. DOI: 10.1016/0167-5699(96)80543-3. View

Lu L, Bonham C, Chambers F, Watkins S, Hoffman R, Simmons R . Induction of nitric oxide synthase in mouse dendritic cells by IFN-gamma, endotoxin, and interaction with allogeneic T cells: nitric oxide production is associated with dendritic cell apoptosis. J Immunol. 1996; 157(8):3577-86. View

Tai X, Toyo-Oka K, Yamamoto N, Yashiro Y, Mu J, Hamaoka T . Expression of an inducible type of nitric oxide (NO) synthase in the thymus and involvement of NO in deletion of TCR-stimulated double-positive thymocytes. J Immunol. 1997; 158(10):4696-703. View

10.

Wilckens T, de Rijk R . Glucocorticoids and immune function: unknown dimensions and new frontiers. Immunol Today. 1997; 18(9):418-24. DOI: 10.1016/s0167-5699(97)01111-0. View

11.

Arnason B, JANKOVIC B, Waksman B, WENNERSTEN C . Role of the thymus in immune reactions in rats. II. Suppressive effect of thymectomy at birth on reactions of delayed (cellular) hypersensitivity and the circulating small lymphocyte. J Exp Med. 1962; 116:177-86. PMC: 2137389. DOI: 10.1084/jem.116.2.177. View

12.

Ben-Nun A, Ron Y, Cohen I . Spontaneous remission of autoimmune encephalomyelitis is inhibited by splenectomy, thymectomy or ageing. Nature. 1980; 288(5789):389-90. DOI: 10.1038/288389a0. View

13.

Gao E, Lo D, Cheney R, Kanagawa O, Sprent J . Abnormal differentiation of thymocytes in mice treated with cyclosporin A. Nature. 1988; 336(6195):176-9. DOI: 10.1038/336176a0. View

14.

MacPhee I, Antoni F, Mason D . Spontaneous recovery of rats from experimental allergic encephalomyelitis is dependent on regulation of the immune system by endogenous adrenal corticosteroids. J Exp Med. 1989; 169(2):431-45. PMC: 2189214. DOI: 10.1084/jem.169.2.431. View

15.

Kosaka H, Matsubara H, Sogoh S, Ogata M, Hamaoka T, Fujiwara H . An in vitro model for cyclosporin A-induced interference of intrathymic clonal elimination. J Exp Med. 1990; 172(1):395-8. PMC: 2188159. DOI: 10.1084/jem.172.1.395. View

16.

Sakaguchi S, Sakaguchi N . Thymus and autoimmunity: capacity of the normal thymus to produce pathogenic self-reactive T cells and conditions required for their induction of autoimmune disease. J Exp Med. 1990; 172(2):537-45. PMC: 2188326. DOI: 10.1084/jem.172.2.537. View

17.

Radomski M, Palmer R, Moncada S . Glucocorticoids inhibit the expression of an inducible, but not the constitutive, nitric oxide synthase in vascular endothelial cells. Proc Natl Acad Sci U S A. 1990; 87(24):10043-7. PMC: 55311. DOI: 10.1073/pnas.87.24.10043. View

18.

Dawson T, Bredt D, Fotuhi M, Hwang P, Snyder S . Nitric oxide synthase and neuronal NADPH diaphorase are identical in brain and peripheral tissues. Proc Natl Acad Sci U S A. 1991; 88(17):7797-801. PMC: 52390. DOI: 10.1073/pnas.88.17.7797. View

19.

Brenan M, Puklavec M . The MRC OX-62 antigen: a useful marker in the purification of rat veiled cells with the biochemical properties of an integrin. J Exp Med. 1992; 175(6):1457-65. PMC: 2119258. DOI: 10.1084/jem.175.6.1457. View

20.

Taylor-Robinson A, Liew F, Severn A, Xu D, McSorley S, Garside P . Regulation of the immune response by nitric oxide differentially produced by T helper type 1 and T helper type 2 cells. Eur J Immunol. 1994; 24(4):980-4. DOI: 10.1002/eji.1830240430. View