The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1997/2/731/ $5.00
The Journal of Experimental Medicine, Volume 185, Number 4, February 17, 1997 731-744

Articles

Induction of the Early Growth Response (Egr) Family of Transcription Factors during Thymic Selection

Hui Shao, Dwight H. Kono, Ling-Yu Chen, Elyssa M. Rubin, and Jonathan Kaye

From the Department of Immunology, The Scripps Research Institute, La Jolla, California 92037

There is little known about the regulation of gene expression during TCR-mediated differentiation of immature CD4+8+ (double positive) thymocytes into mature T cells. Using the DPK CD4+8+thymocyte precursor cell line, we demonstrate that the early growth response-1 gene (Erg-1), encoding a zinc finger transcription factor, is rapidly upregulated after TCR stimulation. We also report that Egr-1 is expressed by a subset of normal double positive thymocytes in the thymic cortex, as well by a majority of medullary single positive thymocytes. Expression of Egr-1 is dramatically reduced in the thymus of major histocompatibility complex knockout mice, but can be induced by anti-CD3 antibody stimulation of isolated thymocytes from these animals. These and other data suggest that high level expression of Egr-1 in the thymus is a consequence of selection. A similar pattern of expression is found for family members Egr-2 and Egr-3. Using the DPK cell line, we also demonstrate that expression of Egr-1, 2, and 3 is dependent upon ras activation, as is the initiation of differentiation to a single positive cell. In contrast, the calcineurin inhibitor cyclosporin A, which inhibits DPK cell differentiation as well as positive selection, inhibits expression of Egr-2 and Egr-3, but not Egr-1. The identification of the Egr family in this context represents the first report of a link between the two known signaling pathways involved in positive selection and downstream transcriptional regulators.

Address correspondence to Dr. Jonathan Kaye, Department of Immunology, IMM-8, The Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, California 92037.

1 Abbreviations used in this paper: CsA, cyclosporin A; Erg-1, early growth response.

H. Shao and D. Kono contributed equally to this work.


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