HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Frank, G. D. Articles by Parnes, J. R. Search for Related Content PubMed PubMed Citation Articles by Frank, G. D. Articles by Parnes, J. R. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene

The Level of CD4 Surface Protein Influences T Cell Selection in the Thymus¹

Gregory D. Frank^*, and Jane R. Parnes^2,

^* Program in Immunology and Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA 94305

During T cell development thymocytes are subjected to positive and negative selection criteria to ensure that the mature T cell repertoire is MHC restricted, yet self tolerant at the same time. The CD4 and CD8 coreceptors are thought to play a crucial role in this developmental process. To elucidate the role of CD4 in T cell selection, we have produced a mouse strain that expresses CD4 at a reduced level. We used homologous recombination in embryonic stem cells to insert neo into the 3' untranslated region of CD4. The resulting mice have a reduction in the percentage of CD4⁺ cells in the thymus and a concomitant increase in CD8⁺ cells. In addition, breeding two individual class II-restricted TCR transgenic mice onto the CD4^low (low level of CD4) mutant background affects the selection of each TCR differentially. In one case (AND TCR transgenic), significantly fewer CD4⁺ cells with the transgenic TCR develop on the CD4^low mutant background, whereas in the other (5C.C7 TCR transgenic), selection to the CD4 lineage is only slightly reduced. These data support the differential avidity model of positive and negative selection. With little or no avidity, the cell succumbs to programmed cell death, low to moderate avidity leads to positive selection, and an avidity above a certain threshold, presumably above one that would lead to autoreactivity in the periphery, results in clonal deletion. These data also support the idea that a minimum avidity threshold for selection exists and that CD4 plays a crucial role in determining this avidity.

This article has been cited by other articles:

				O. Boyer, G. Marodon, J. L. Cohen, L. Lejeune, T. Irinopoulou, R. Liblau, P. Bruneval, and D. Klatzmann Human CD4 Expression at the Late Single-Positive Stage of Thymic Development Supports T Cell Maturation and Peripheral Export in CD4-Deficient Mice J. Immunol., October 15, 2002; 169(8): 4347 - 4353. [Abstract] [Full Text] [PDF]

				N. G. Singer, D. A. Fox, T. M. Haqqi, L. Beretta, J. S. Endres, S. Prohaska, J. R. Parnes, J. Bromberg, and R. M. Sramkoski CD6: expression during development, apoptosis and selection of human and mouse thymocytes Int. Immunol., June 1, 2002; 14(6): 585 - 597. [Abstract] [Full Text] [PDF]

				G. J. Wiegers, I. E. M. Stec, W. E. F. Klinkert, and J. M. H. M. Reul Glucocorticoids Regulate TCR-Induced Elevation of CD4: Functional Implications J. Immunol., June 15, 2000; 164(12): 6213 - 6220. [Abstract] [Full Text] [PDF]

				E. A. Mostaghel, J. M. Riberdy, D. A. Steeber, and C. Doyle Coreceptor-Independent T Cell Activation in Mice Expressing MHC Class II Molecules Mutated in the CD4 Binding Domain J. Immunol., December 15, 1998; 161(12): 6559 - 6566. [Abstract] [Full Text] [PDF]