An in Vitro Model for Cyclosporin A-induced Interference of Intrathymic Clonal Elimination

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 1990 Jul 1

PMID 2113566

Citations 2

Authors

H Kosaka

H Matsubara

S Sogoh

M Ogata

T Hamaoka

H Fujiwara

Affiliations

Soon will be listed here.

Abstract

The effects of cyclosporin A (CsA) on influencing the intrathymic clonal deletion were investigated by using our established thymic stromal cell clone with capacities to express Ia antigens and to produce a unique T cell growth factor. The following were revealed: (a) T cell clone with a given specificity was killed on the Ia+ stromal cell monolayer in the presence of the relevant antigens, a process depending on T cell receptor (TCR) stimulation; and (b) CsA allowed the T cell clone to continuously proliferate even during TCR stimulation by virtue of the stromal cell-derived T cell growth factor. This paper describes an in vitro model of a mechanism by which CsA is responsible for the generation of normally "forbidden" T cell clones.

Citing Articles

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.

DOWNING J, Virag L, Jones I Immunology. 1998; 95(1):148-55.

PMID: 9767470 PMC: 1364389. DOI: 10.1046/j.1365-2567.1998.00576.x.

Demonstration of large-scale migration of cortical thymocytes to peripheral lymphoid tissues in cyclosporin A-treated rats.

Zadeh H, Goldschneider I J Exp Med. 1993; 178(1):285-93.

PMID: 8315384 PMC: 2191078. DOI: 10.1084/jem.178.1.285.

References

Tutschka P, Beschorner W, Allison A, BURNS W, SANTOS G . Use of cyclosporin A in allogeneic bone marrow transplantation in the rat. Nature. 1979; 280(5718):148-51. DOI: 10.1038/280148a0. View

Bolton C, Allsopp G, Cuzner M . The effect of cyclosporin A on the adoptive transfer of experimental allergic encephalomyelitis in the Lewis rat. Clin Exp Immunol. 1982; 47(1):127-32. PMC: 1536363. View

Stiller C, Dupre J, Gent M, Jenner M, Keown P, Laupacis A . Effects of cyclosporine immunosuppression in insulin-dependent diabetes mellitus of recent onset. Science. 1984; 223(4643):1362-7. DOI: 10.1126/science.6367043. View

Shevach E . The effects of cyclosporin A on the immune system. Annu Rev Immunol. 1985; 3:397-423. DOI: 10.1146/annurev.iy.03.040185.002145. View

Sorokin R, Kimura H, Schroder K, Wilson D, Wilson D . Cyclosporine-induced autoimmunity. Conditions for expressing disease, requirement for intact thymus, and potency estimates of autoimmune lymphocytes in drug-treated rats. J Exp Med. 1986; 164(5):1615-25. PMC: 2188452. DOI: 10.1084/jem.164.5.1615. View

Kappler J, Roehm N, Marrack P . T cell tolerance by clonal elimination in the thymus. Cell. 1987; 49(2):273-80. DOI: 10.1016/0092-8674(87)90568-x. View

Kosaka H, Ogata M, Hikita I, Maruo S, Sugihara S, Matsubara H . Model for clonal elimination in the thymus. Proc Natl Acad Sci U S A. 1989; 86(10):3773-7. PMC: 287222. DOI: 10.1073/pnas.86.10.3773. View

Kisielow P, Bluthmann H, Staerz U, Steinmetz M, von Boehmer H . Tolerance in T-cell-receptor transgenic mice involves deletion of nonmature CD4+8+ thymocytes. Nature. 1988; 333(6175):742-6. DOI: 10.1038/333742a0. View

Sato S, Ogata M, Sano H, Mizushima Y, Muramatsu M, Doi H . Thymic stroma-derived T-cell growth factor (TSTGF): II. Biochemical and functional characterization. J Leukoc Biol. 1988; 44(3):149-57. DOI: 10.1002/jlb.44.3.149. View

10.

Jenkins M, Schwartz R, Pardoll D . Effects of cyclosporine A on T cell development and clonal deletion. Science. 1988; 241(4873):1655-8. DOI: 10.1126/science.241.4873.1655. View

11.

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

12.

Ogata M, Matsubara H, Takai Y, Kosaka H, Katagiri T, Sano H . Capacities of a newly established thymic stromal cell clone to express Ia antigens and to produce interleukin-6, colony-stimulating factor, and thymic stroma-derived T-cell growth factor. J Leukoc Biol. 1989; 45(1):69-78. DOI: 10.1002/jlb.45.1.69. View

13.

Mizushima Y, Saitoh M, Ogata M, Kosaka H, Tatsumi Y, Kiyotaki C . Thymic stroma-derived T cell growth factor (TSTGF). IV. Capacity of TSTGF to promote the growth of L3T4- Lyt-2- thymocytes by synergy with phorbol myristate acetate or various IL. J Immunol. 1989; 142(4):1195-202. View

14.

Sakaguchi S, Sakaguchi N . Thymus and autoimmunity. Transplantation of the thymus from cyclosporin A-treated mice causes organ-specific autoimmune disease in athymic nude mice. J Exp Med. 1988; 167(4):1479-85. PMC: 2188920. DOI: 10.1084/jem.167.4.1479. View