Characterization of Extrathymic CD8 Alpha Beta T Cells in the Liver and Intestine in TAP-1 Deficient Mice

Overview

Journal Immunology

Specialty Allergy & Immunology

Date 2003 Jun 17

PMID 12807479

Citations 3

Authors

Chika Tsukada

Chikako Miyaji

Hiroki Kawamura

Ryoko Miyakawa

Hisashi Yokoyama

Yuiko Ishimoto

Shinobu Miyazawa

Hisami Watanabe

Toru Abo

Affiliations

Soon will be listed here.

Abstract

TAP-1 deficient (-/-) mice cannot transport MHC class I antigens onto the cell surface, which results in failure of the generation of CD8+ T cells in the thymus. In a series of recent studies, it has been proposed that extrathymic T cells are generated in the liver and at other extrathymic sites (e.g. the intestine). It was therefore investigated whether CD8+ extrathymic T cells require an interaction with MHC class I antigens for their differentiation in TAP-1(-/-) mice. Although CD8+ thymically derived T cells were confirmed to be absent in the spleen as well as in the thymus, CD8 alpha beta+ T cells were abundant in the livers and intestines of TAP-1(-/-) mice. These CD8+ T cells expanded in the liver as a function of age and were mainly confined to a NK1.1-CD3int population which is known to be truly of extrathymic origin. Hepatic lymphocytes, which contained CD8+ T cells and which were isolated from TAP-1(-/-) mice (H-2b), responded to neither mutated MHC class I antigens (bm1) nor allogeneic MHC class I antigens (H-2d) in in vitro mixed lymphocyte cultures. However, the results from repeated in vivo stimulations with alloantigens (H-2d) were interesting. Allogeneic cytotoxicity was induced in liver lymphocytes in TAP-1(-/-) mice, although the magnitude of cytotoxicity was lower than that of liver lymphocytes in immunized B6 mice. All allogeneic cytotoxicity disappeared with the elimination of CD8+ cells in TAP-1(-/-) mice. These results suggest that the generation and function of CD8+ extrathymic T cells are independent of the existence of the MHC class I antigens of the mouse but have a limited allorecognition ability.

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References

Tilloy F, Di Santo J, Bendelac A, Lantz O . Thymic dependence of invariant V alpha 14+ natural killer-T cell development. Eur J Immunol. 1999; 29(10):3313-8. DOI: 10.1002/(SICI)1521-4141(199910)29:10<3313::AID-IMMU3313>3.0.CO;2-8. View

Van Kaer L, Ashton-Rickardt P, Ploegh H, Tonegawa S . TAP1 mutant mice are deficient in antigen presentation, surface class I molecules, and CD4-8+ T cells. Cell. 1992; 71(7):1205-14. DOI: 10.1016/s0092-8674(05)80068-6. View

Bannai M, Oya H, Kawamura T, Naito T, Shimizu T, Kawamura H . Disparate effect of beige mutation on cytotoxic function between natural killer and natural killer T cells. Immunology. 2000; 100(2):165-9. PMC: 2327008. DOI: 10.1046/j.1365-2567.2000.00040.x. View

Weerasinghe A, Sekikawa H, Watanabe H, Mannoor K, Morshed S, Halder R . Association of intermediate T cell receptor cells, mainly their NK1.1(-) subset, with protection from malaria. Cell Immunol. 2001; 207(1):28-35. DOI: 10.1006/cimm.2000.1737. View

Gabriel H, Schmitt B, Kindermann W . Age-related increase of CD45RO+ lymphocytes in physically active adults. Eur J Immunol. 1993; 23(10):2704-6. DOI: 10.1002/eji.1830231049. View

Callahan J, Kappler J, Marrack P . Unexpected expansions of CD8-bearing cells in old mice. J Immunol. 1993; 151(12):6657-69. View

Glas R, Ohlen C, Hoglund P, Karre K . The CD8+ T cell repertoire in beta 2-microglobulin-deficient mice is biased towards reactivity against self-major histocompatibility class I. J Exp Med. 1994; 179(2):661-72. PMC: 2191377. DOI: 10.1084/jem.179.2.661. View

Aldrich C, Ljunggren H, Van Kaer L, Ashton-Rickardt P, Tonegawa S, Forman J . Positive selection of self- and alloreactive CD8+ T cells in Tap-1 mutant mice. Proc Natl Acad Sci U S A. 1994; 91(14):6525-8. PMC: 44235. DOI: 10.1073/pnas.91.14.6525. View

Holcombe H, Castano A, Cheroutre H, Teitell M, Maher J, Peterson P . Nonclassical behavior of the thymus leukemia antigen: peptide transporter-independent expression of a nonclassical class I molecule. J Exp Med. 1995; 181(4):1433-43. PMC: 2191972. DOI: 10.1084/jem.181.4.1433. View

10.

Kawachi Y, Watanabe H, Moroda T, Haga M, Iiai T, Hatakeyama K . Self-reactive T cell clones in a restricted population of interleukin-2 receptor beta+ cells expressing intermediate levels of the T cell receptor in the liver and other immune organs. Eur J Immunol. 1995; 25(8):2272-8. DOI: 10.1002/eji.1830250824. View

11.

Watanabe H, Miyaji C, Kawachi Y, Iiai T, Ohtsuka K, Iwanage T . Relationships between intermediate TCR cells and NK1.1+ T cells in various immune organs. NK1.1+ T cells are present within a population of intermediate TCR cells. J Immunol. 1995; 155(6):2972-83. View

12.

Brutkiewicz R, Bennink J, Yewdell J, Bendelac A . TAP-independent, beta 2-microglobulin-dependent surface expression of functional mouse CD1.1. J Exp Med. 1995; 182(6):1913-9. PMC: 2192266. DOI: 10.1084/jem.182.6.1913. View

13.

Fujiura Y, Kawaguchi M, Kondo Y, Obana S, Yamamoto H, Nanno M . Development of CD8 alpha alpha+ intestinal intraepithelial T cells in beta 2-microglobulin- and/or TAP1-deficient mice. J Immunol. 1996; 156(8):2710-5. View

14.

Ljunggren H, Glas R, Sandberg J, Karre K . Reactivity and specificity of CD8+ T cells in mice with defects in the MHC class I antigen-presenting pathway. Immunol Rev. 1996; 151:123-48. DOI: 10.1111/j.1600-065x.1996.tb00706.x. View

15.

Moroda T, Iiai T, Kawachi Y, Kawamura T, Hatakeyama K, Abo T . Restricted appearance of self-reactive clones into T cell receptor intermediate cells in neonatally thymectomized mice with autoimmune disease. Eur J Immunol. 1996; 26(12):3084-91. DOI: 10.1002/eji.1830261239. View

16.

Moroda T, Kawachi Y, Iiai T, Tsukahara A, Suzuki S, Tada T . Self-reactive forbidden clones are confined to pathways of intermediate T-cell receptor cell differentiation even under immunosuppressive conditions. Immunology. 1997; 91(1):88-94. PMC: 1364039. DOI: 10.1046/j.1365-2567.1997.00222.x. View

17.

Tsukahara A, Seki S, Iiai T, Moroda T, Watanabe H, Suzuki S . Mouse liver T cells: their change with aging and in comparison with peripheral T cells. Hepatology. 1997; 26(2):301-9. DOI: 10.1002/hep.510260208. View

18.

Kawamura H, Kawamura T, Kokai Y, Mori M, Matsuura A, Oya H . Expansion of extrathymic T cells as well as granulocytes in the liver and other organs of granulocyte-colony stimulating factor transgenic mice: why they lost the ability of hybrid resistance. J Immunol. 1999; 162(10):5957-64. View

19.

Minagawa M, Narita J, Tada T, Maruyama S, Shimizu T, Bannai M . Mechanisms underlying immunologic states during pregnancy: possible association of the sympathetic nervous system. Cell Immunol. 1999; 196(1):1-13. DOI: 10.1006/cimm.1999.1541. View

20.

Halder R, Kawamura T, Bannai M, Watanabe H, Kawamura H, Mannoor M . Intensive generation of NK1.1- extrathymic T cells in the liver by injection of bone marrow cells isolated from mice with a mutation of polymorphic major histocompatibility complex antigens. Immunology. 2001; 102(4):450-9. PMC: 1783195. DOI: 10.1046/j.1365-2567.2001.01210.x. View