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International Immunology, Vol. 11, No. 10, 1595-1600, October 1999
© 1999 Japanese Society for Immunology

Positive selection of thymocytes induced by gene transfer: MHC class II-mediated selection of CD8 lineage cells

Ronald Rooke, Caroline Waltzinger, Christophe Benoist and Diane Mathis

Institut de Génétique et de Biologie Moléculaire et Cellulaire (CNRS/INSERM/ULP), 67404 Illkirch, CU de Strasbourg, France

Correspondence to: C. Benoist

Recombinant adenovirus vectors are powerful tools for inducing de novo gene expression in vivo. Here we have exploited them to study the specificity of CD4/CD8 lineage commitment during thymocyte positive selection, transferring MHC class II genes directly into thymi of mice deficient in both class I and II molecules. Expression of class II molecules was induced on cortical stroma, provoking the selection of a large population of mature CD4+CD8– cells, as expected, but also of a significant number of CD4–CD8+ cells. The latter constituted a diverse population, containing both immature precursors and, though less frequent, cells that were mature according to several criteria. CD4–CD8+ cells appeared with the same kinetics as their CD4+CD8– counterparts, but tended to be more prevalent at early times or when thymocyte reconstitution was only modest. These observations, derived from a dynamic selection system, indicate that CD4/CD8 lineage commitment is not irredeemably linked to the class of MHC molecule driving positive selection, a conclusion most compatible with selective models of commitment.

Keywords: adenovirus, gene therapy, knockout mice, lymphocyte repertoire, MHC class II genes, T cell differentiation

Transmitting editor: T. Sasazuki


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