Thymocyte antigens do not induce tolerance in the CD4+ T cell compartment

Kanchan G. Jhaver, Phillip Chandler, Elizabeth Simpson, Andrew L. Mellor

Research output: Contribution to journalArticle

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Abstract

Thymocytes fail to tolerize the developing T cell repertoire to self MHC class I (MHC I) Ags because transgenic (CD2Kb) mice expressing H-2Kb solely in lymphoid cell lineages reject skin grafts mismatched only for H-2Kb. In this study, we examined why thymocytes fail to tolerize the T cell repertoire to self MHC I Ags. The ability of CD2Kb mice to reject H-2Kb skin grafts was age dependent because CD2Kb mice older than 20 wk accepted skin grafts. T cells from younger CD2Kb mice proliferated, but did not develop cytotoxic functions in vitro in response to H-2Kb. Proliferative responses were dominated by H-2Kb-specific, CD4+ T cells rather than CD8+ T cells. Representative CD4+ T cell clones from CD2Kb mice were MHC II restricted and recognized processed H-2Kb. TCR transgenic mice were generated from one CD4+ T cell clone (361) to monitor development of H-2Kb-specific immature thymocytes when all thymic cells or lymphoid cell lineages only expressed H- 2Kb. Thymocyte precursors were not eliminated and mice were not tolerant to H-2Kb when Tg361 TCR transgenic mice were intercrossed with CD2Kb mice. In contrast, all thymocyte precursors were eliminated efficiently in thymic microenvironments in which all cells expressed H-2Kb. We conclude that self MHC I Ags expressed exclusively in thymocytes do not induce T cell tolerance because presentation of processed self MHC I Ags on self MHC II molecules fails to induce negative selection of CD4+ T cell precursors. This suggests that some self Ags are effectively compartmentalized and cannot induce self- tolerance in the T cell repertoire.

Original languageEnglish (US)
Pages (from-to)4851-4858
Number of pages8
JournalJournal of Immunology
Volume163
Issue number9
StatePublished - Nov 6 1999

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Thymocytes
T-Lymphocytes
Antigens
Transgenic Mice
Cell Lineage
Transplants
Skin
Clone Cells
Lymphocytes
T-Lymphoid Precursor Cells
Self Tolerance

ASJC Scopus subject areas

  • Immunology

Cite this

Jhaver, K. G., Chandler, P., Simpson, E., & Mellor, A. L. (1999). Thymocyte antigens do not induce tolerance in the CD4+ T cell compartment. Journal of Immunology, 163(9), 4851-4858.

Thymocyte antigens do not induce tolerance in the CD4+ T cell compartment. / Jhaver, Kanchan G.; Chandler, Phillip; Simpson, Elizabeth; Mellor, Andrew L.

In: Journal of Immunology, Vol. 163, No. 9, 06.11.1999, p. 4851-4858.

Research output: Contribution to journalArticle

Jhaver, KG, Chandler, P, Simpson, E & Mellor, AL 1999, 'Thymocyte antigens do not induce tolerance in the CD4+ T cell compartment', Journal of Immunology, vol. 163, no. 9, pp. 4851-4858.
Jhaver KG, Chandler P, Simpson E, Mellor AL. Thymocyte antigens do not induce tolerance in the CD4+ T cell compartment. Journal of Immunology. 1999 Nov 6;163(9):4851-4858.
Jhaver, Kanchan G. ; Chandler, Phillip ; Simpson, Elizabeth ; Mellor, Andrew L. / Thymocyte antigens do not induce tolerance in the CD4+ T cell compartment. In: Journal of Immunology. 1999 ; Vol. 163, No. 9. pp. 4851-4858.
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