Overexpression of CD3η during thymic development does not alter the negative selection process

Rebecca E. Hussey, Linda K. Clayton, Andrew Diener, David J. McConkey, Frank D. Howard, Hans Reimer Rodewald, Luciano D'Adamio, Fredericka Dallenbach, Harald Stein, Emmett V. Schmidt, Shigeo Koyasu, Ellis L. Reinherz

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

To elucidate the role of CD3η in thymic development and to determine whether CD3η is involved in the negative selection process, CD3η was overexpressed >100 fold in transgenic (tg) mice using a Thy-1 promoter and regulatory elements. CD3η was readily observed in the majority of cortical thymocytes and in a fraction of medullary thymocytes in tg mice by immunohistochemical staining with an anti-CD3η-specific mAb. In contrast, endogenous CD3η levels were too low to detect in normal littermates. Flow cytometric analysis demonstrated an increased level of TCR on thymocytes with intermediate TCR density in tg animals and parallel biochemical studies showed a marked increased in TCR-associated CD3ζ-η heterodimers and CD3η-η homodimers relative to controls. Despite this change in surface TCR phenotype, there was no significant alteration in the total numbers or proportion of CD4+CD8+ double-positive or CD4+CD8- or CD4-CD8+ single-positive thymocytes or peripheral T cells. Percentages of SP Vβ5, Vβ6, and Vβ8 thymocytes in tg animals were unaltered compared to normal littermates when backcrossed either to C57BL/6 (H-2b) or DBA/2 (H-2d) backgrounds. Furthermore, induction of DNA fragmentation with anti-CD3ε mAb treatment in vivo was not significantly different for tg and normal littermates. Collectively, these data imply that CD3η is not a limiting component of the negative selection process.

Original languageEnglish (US)
Pages (from-to)1183-1194
Number of pages12
JournalJournal of Immunology
Volume150
Issue number4
StatePublished - 1993
Externally publishedYes

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Thymocytes
Genetically Modified Animals
Transgenic Mice
DNA Fragmentation
Staining and Labeling
T-Lymphocytes
Phenotype

ASJC Scopus subject areas

  • Immunology

Cite this

Hussey, R. E., Clayton, L. K., Diener, A., McConkey, D. J., Howard, F. D., Rodewald, H. R., ... Reinherz, E. L. (1993). Overexpression of CD3η during thymic development does not alter the negative selection process. Journal of Immunology, 150(4), 1183-1194.

Overexpression of CD3η during thymic development does not alter the negative selection process. / Hussey, Rebecca E.; Clayton, Linda K.; Diener, Andrew; McConkey, David J.; Howard, Frank D.; Rodewald, Hans Reimer; D'Adamio, Luciano; Dallenbach, Fredericka; Stein, Harald; Schmidt, Emmett V.; Koyasu, Shigeo; Reinherz, Ellis L.

In: Journal of Immunology, Vol. 150, No. 4, 1993, p. 1183-1194.

Research output: Contribution to journalArticle

Hussey, RE, Clayton, LK, Diener, A, McConkey, DJ, Howard, FD, Rodewald, HR, D'Adamio, L, Dallenbach, F, Stein, H, Schmidt, EV, Koyasu, S & Reinherz, EL 1993, 'Overexpression of CD3η during thymic development does not alter the negative selection process', Journal of Immunology, vol. 150, no. 4, pp. 1183-1194.
Hussey RE, Clayton LK, Diener A, McConkey DJ, Howard FD, Rodewald HR et al. Overexpression of CD3η during thymic development does not alter the negative selection process. Journal of Immunology. 1993;150(4):1183-1194.
Hussey, Rebecca E. ; Clayton, Linda K. ; Diener, Andrew ; McConkey, David J. ; Howard, Frank D. ; Rodewald, Hans Reimer ; D'Adamio, Luciano ; Dallenbach, Fredericka ; Stein, Harald ; Schmidt, Emmett V. ; Koyasu, Shigeo ; Reinherz, Ellis L. / Overexpression of CD3η during thymic development does not alter the negative selection process. In: Journal of Immunology. 1993 ; Vol. 150, No. 4. pp. 1183-1194.
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