Details

Autor(en) / Beteiligte

• Müller, Klaus‐Peter
• Kyewski, Bruno A.

Titel

T cell receptor targeting to thymic cortical epithelial cells in vivo induces survival, activation and differentiation of immature thymocytes

Ist Teil von

• European journal of immunology, 1993-07, Vol.23 (7), p.1661-1670

Ort / Verlag

Weinheim: WILEY‐VCH Verlag GmbH

Erscheinungsjahr

1993

Quelle

Wiley Online Journals

Beschreibungen/Notizen

• We report that targeting of T cell receptors (TcR) to non‐major histocompatibility complex (MHC) molecules on thymic cortical epithelial cells by hybrid antibodies in vivo and in fetal thymic organ cultures results in phenotypic and functional differentiation of thymocytes. A single pulse with hybrid antibodies rescues immature, CD4/8 double‐positive thymocytes from their programmed death in vivo, induces expression of the early activation antigen CD69 followed by TcR up‐regulation, concomitant down‐regulation of CD8 or CD4 and their conversion to functional mature T cells by day 3. This temporal sequence of maturation only affects small thymocytes without co‐induction of blastogenesis. TcR targeting to MHC class II‐positive epithelial cells predominantly induces CD4‐positive T cells. This generation of CD4 single‐positive T cells occurs also in MHC class II‐deficient mice and thus is independent of CD4‐MHC class II interactions. Moreover, in the presence of a specific deleting antigen (Mls 1a),TcR targeting results in transient activation of immature thymocytes, however, not in subsequent TcR (Vβ6) up‐regulation and development of single‐positive T cells. Our findings imply that TcR cross‐linking to cortical epithelial cells is sufficient to confer a differentiation signal to immature thymocytes. Futhermore, this approach distinguishes two independent TcR‐mediated intrathymic events: activation and subsequent deletion of the same thymocyte subset.