Peripheral deletion of mature CD8+ antigen-specific T cells after in vivo exposure to male antigen

Li Zhang, Diego R Martin, Wai Ping Fung-Leung, Hung Sia Teh, Richard G. Miller

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

It has been well established that T cell tolerance to self Ag occurs primarily via clonal deletion of immature thymocytes in the thymus. Evidence also exists that there are additional mechanisms operative on mature T cells for establishing and maintaining tolerance in the periphery. To follow the fate of mature Ag-specific T cells in vivo, we used female transgenic mice, which contain a large population of male H-Y Ag-specific T cells that can be identified by immunostaining with mAb directed against CDS and the transgenic TCR. H-Y Ag was introduced into these mice by injecting Ag-bearing male lymphocytes using conditions known to induce CTL precursor response reduction. The number of Ag-reactive CD8+ transgenic T cells in the periphery started to decrease after 2 days of in vivo exposure to male Ag. Decline was maximum (up to 80% of total) by 7 days, and stayed at this level for at least 6 wk. CD4+ cells and those CD8+ cells that did not carry the transgenic TCR were not affected. Most or all of the remaining Ag-reactive CD8+ cells in the periphery were fully responsive when stimulated by male Ag in vitro. Maturation of transgenic T cells in the thymus of injected mice remained the same as that of control animals. Our data provide direct evidence that mature Ag-reactive CD8+ cells are susceptible to clonal deletion in the periphery when exposed to the Ag in vivo. These findings suggest the presence of two types of APC in the periphery: stimulatory APC (e.g., macrophages and dendritic cells) required for initiating an active immune response; and functionally deleting APC (or veto cells) capable of deleting mature T lymphocytes that recognize Ag presented on their surface. Functionally deleting APC that present self Ag to peripheral T cells may provide a fail-safe mechanism against autoreactive cells that escaped deletion during differentiation in the thymus.

Original languageEnglish (US)
Pages (from-to)3740-3745
Number of pages6
JournalJournal of Immunology
Volume148
Issue number12
StatePublished - Jun 15 1992
Externally publishedYes

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CD8 Antigens
T-Lymphocytes
Antigens
Clonal Deletion
Thymus Gland
Active Immunity
Thymocytes
Dendritic Cells
Transgenic Mice
Macrophages
Lymphocytes

ASJC Scopus subject areas

  • Immunology

Cite this

Zhang, L., Martin, D. R., Fung-Leung, W. P., Teh, H. S., & Miller, R. G. (1992). Peripheral deletion of mature CD8+ antigen-specific T cells after in vivo exposure to male antigen. Journal of Immunology, 148(12), 3740-3745.

Peripheral deletion of mature CD8+ antigen-specific T cells after in vivo exposure to male antigen. / Zhang, Li; Martin, Diego R; Fung-Leung, Wai Ping; Teh, Hung Sia; Miller, Richard G.

In: Journal of Immunology, Vol. 148, No. 12, 15.06.1992, p. 3740-3745.

Research output: Contribution to journalArticle

Zhang, L, Martin, DR, Fung-Leung, WP, Teh, HS & Miller, RG 1992, 'Peripheral deletion of mature CD8+ antigen-specific T cells after in vivo exposure to male antigen', Journal of Immunology, vol. 148, no. 12, pp. 3740-3745.
Zhang, Li ; Martin, Diego R ; Fung-Leung, Wai Ping ; Teh, Hung Sia ; Miller, Richard G. / Peripheral deletion of mature CD8+ antigen-specific T cells after in vivo exposure to male antigen. In: Journal of Immunology. 1992 ; Vol. 148, No. 12. pp. 3740-3745.
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