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By
From the Basel Institute for Immunology, CH-4058 Basel, Switzerland
It is well established that lymphoid dendritic cells (DC) play an important role in the immune
system. Beside their role as potent inducers of primary T cell responses, DC seem to play a crucial part as major histocompatibility complex (MHC) class II+ "interdigitating cells" in the thymus during thymocyte development. Thymic DC have been implicated in tolerance induction
and also by some authors in inducing major histocompatibility complex restriction of thymocytes. Most of our knowledge about thymic DC was obtained using highly invasive and
manipulatory experimental protocols such as thymus reaggregation cultures, suspension cultures, thymus grafting, and bone marrow reconstitution experiments. The DC used in those
studies had to go through extensive isolation procedures or were cultured with recombinant
growth factors. Since the functions of DC after these in vitro manipulations have been reported
to be not identical to those of DC in vivo, we intended to establish a system that would allow
us to investigate DC function avoiding artificial interferences due to handling. Here we present
a transgenic mouse model in which we targeted gene expression specifically to DC. Using the
CD11c promoter we expressed MHC class II I-E molecules specifically on DC of all tissues, but
not on other cell types. We report that I-E expression on thymic DC is sufficient to negatively select I-E reactive CD4+ T cells, and to a less complete extent, CD8+ T cells. In contrast, if only DC
expressed I-E in a class II-deficient background, positive selection of CD4+ T cells could not
be observed. Thus negative, but not positive, selection events can be induced by DC in vivo.
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