TARGETED EXPRESSION OF MAJOR HISTOCOMPATIBILITY COMPLEX (MHC) CLASS-II MOLECULES DEMONSTRATES THAT DENDRITIC CELLS CAN INDUCE NEGATIVE BUT NOT POSITIVE SELECTION OF THYMOCYTES IN-VIVO
T. Brocker et al., TARGETED EXPRESSION OF MAJOR HISTOCOMPATIBILITY COMPLEX (MHC) CLASS-II MOLECULES DEMONSTRATES THAT DENDRITIC CELLS CAN INDUCE NEGATIVE BUT NOT POSITIVE SELECTION OF THYMOCYTES IN-VIVO, The Journal of experimental medicine, 185(3), 1997, pp. 541-550
It is well established that lymphoid dendritic cells (DC) play an impo
rtant 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 h
istocompatibility complex (MHC) class II+ ''interdigitating cells'' in
the thymus during thymocyte development. Thymic DC have been implicat
ed in tolerance induction and also by some authors in inducing major h
istocompatibility complex restriction of thymocytes. Most of our knowl
edge about thymic DC was obtained using highly invasive and manipulato
ry experimental protocols such as thymus reaggregation cultures, suspe
nsion cultures, thymus grafting, and bone marrow reconstitution experi
ments. The DC used in those studies had to go through extensive isolat
ion procedures or were cultured with recombinant growth factors. Since
the functions of DC after these in vitro manipulations have been repo
rted to be not identical to those of DC in vivo, we intended to establ
ish a system that would allow us to investigate DC function avoiding a
rtificial interferences due to handling. Here we present a transgenic
mouse model in which we targeted gene expression specifically to DC. U
sing the CD11c promoter we expressed MHC class II I-E molecules specif
ically on DC of all tissues, but not on other cell types. We report th
at 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 backgr
ound, positive selection of CD4(+) T cells could not be observed. Thus
negative, but not positive, selection events can be induced by DC in
vivo.