The Journal of Immunology, Vol 159, Issue 10 4907-4912, Copyright © 1997 by American Association of Immunologists

ARTICLES

Appropriate developmental expression of human CD8 beta in transgenic mice

LJ Kieffer, L Yan, JH Hanke and PB Kavathas
Department of Laboratory Medicine, Yale University, New Haven, CT 06520- 8035, USA.

The human CD8 glycoprotein is expressed either as an alpha beta heterodimer or as an alpha alpha homodimer on thymocytes, mature T cells, and subpopulations of intestinal intraepithelial lymphocytes (IELs). The homodimeric form of CD8 is exclusively expressed on TCR gamma delta IELs and on subsets of NK cells and TCR alpha beta IELs. To understand the molecular mechanisms by which these genes are regulated, we created transgenic mice with a 95-kb human genomic DNA fragment containing the entire CD8 beta gene as well as a cluster of tissue- specific DNase I-hypersensitive sites 7 to 10 kb upstream of the gene. These sites were present in CD8 alpha beta+- but not CD8 alpha beta- T cell lines nor in a B cell line. We found that transgenic mice had correct developmental expression of human CD8 beta on thymocytes and mature CD8+ cells and no expression on mature CD4+ T cells or B cells. Interestingly, the percentage of mouse CD8 alpha+ cells that were human CD8 beta+ varied, depending on the founder line, from 4 to 88%, whereas the percentage among siblings was similar, indicative of a variegated phenotype resulting from site of integration effects. Expression was also observed on intestinal IELs, but only on those expressing the TCR alpha beta receptor and not the TCR gamma delta cells, which exclusively express CD8 alpha alpha. Of the TCR alpha beta+ cells, the transgene was expressed in both the CD8 alpha alpha and alpha beta subpopulations. These results indicate that this 95-kb fragment affords developmentally correct expression of the human CD8 beta gene on thymus- derived T cells in transgenic animals. Therefore, CD8 lineage-specific regulatory sequences must be located within the fragment.

This article has been cited by other articles:

				E. A. Jones and R. A. Flavell Distal Enhancer Elements Transcribe Intergenic RNA in the IL-10 Family Gene Cluster J. Immunol., December 1, 2005; 175(11): 7437 - 7446. [Abstract] [Full Text] [PDF]

				T.-Y. Roh, S. Cuddapah, and K. Zhao Active chromatin domains are defined by acetylation islands revealed by genome-wide mapping Genes & Dev., March 1, 2005; 19(5): 542 - 552. [Abstract] [Full Text] [PDF]

				L. J. Kieffer, J. M. Greally, I. Landres, S. Nag, Y. Nakajima, T. Kohwi-Shigematsu, and P. B. Kavathas Identification of a Candidate Regulatory Region in the Human CD8 Gene Complex by Colocalization of DNase I Hypersensitive Sites and Matrix Attachment Regions Which Bind SATB1 and GATA-3 J. Immunol., April 15, 2002; 168(8): 3915 - 3922. [Abstract] [Full Text] [PDF]

				L. Devine, L. J. Kieffer, V. Aitken, and P. B. Kavathas Human CD8{beta}, But Not Mouse CD8{beta}, Can Be Expressed in the Absence of CD8{alpha} as a {beta}{beta} Homodimer J. Immunol., January 15, 2000; 164(2): 833 - 838. [Abstract] [Full Text] [PDF]

				Y. R. Carrasco, C. Trigueros, A. R. Ramiro, V. G. de Yebenes, and M. L. Toribio beta -Selection Is Associated With the Onset of CD8beta Chain Expression on CD4+CD8alpha alpha + Pre-T Cells During Human Intrathymic Development Blood, November 15, 1999; 94(10): 3491 - 3498. [Abstract] [Full Text] [PDF]

				M.A. Bender, A. Reik, J. Close, A. Telling, E. Epner, S. Fiering, R. Hardison, and M. Groudine Description and Targeted Deletion of 5' Hypersensitive Site 5 and 6 of the Mouse beta -Globin Locus Control Region Blood, December 1, 1998; 92(11): 4394 - 4403. [Abstract] [Full Text] [PDF]