CD4+ CD25+ regulatory T cells control T helper cell type 1 responses to foreign antigens induced by mature dendritic cells in vivo.

Recent evidence suggests that in addition to their well known stimulatory properties, dendritic cells (DCs) may play a major role in peripheral tolerance. It is still unclear whether a distinct subtype or activation status of DC exists that promotes the differentiation of suppressor rather than effector T cells from naive precursors. In this work, we tested whether the naturally occurring CD4+ CD25+ regulatory T cells (Treg) may control immune responses induced by DCs in vivo. We characterized the immune response induced by adoptive transfer of antigen-pulsed mature DCs into mice depleted or not of CD25+ cells. We found that the development of major histocompatibility complex class I and II-restricted interferon gamma-producing cells was consistently enhanced in the absence of Treg. By contrast, T helper cell (Th)2 priming was down-regulated in the same conditions. This regulation was independent of interleukin 10 production by DCs. Of note, splenic DCs incubated in vitro with Toll-like receptor ligands (lipopolysaccharide or CpG) activated immune responses that remained sensitive to Treg function. Our data further show that mature DCs induced higher cytotoxic activity in CD25-depleted recipients as compared with untreated hosts. We conclude that Treg naturally exert a negative feedback mechanism on Th1-type responses induced by mature DCs in vivo.

Characterization of the morphonuclear features and DNA ploidy of typical and atypical carcinoids and small cell carcinomas of the lung

The authors analyzed several cytomorphonuclear parameters related to chromatin distribution and DNA ploidy in typical and atypical carcinoids and in small cell lung cancers. Nuclear measurements and analysis were performed with a SAMBA 200 (TITN, Grenoble, France) cell image processor with software allowing the discrimination of parameters computed on cytospin preparations of Feulgen-stained nuclei extracted from deparaffinized tumor tissues. The authors' results indicate a significant increase in DNA content--assessed by integrated optical density (IOD)--from typical carcinoids to small cell lung carcinomas, with atypical carcinoids showing an intermediate value. Parameters related to hyperchromatism (short and long run length and variance of optical density) also characterize the atypical carcinoids as being intermediate between typical carcinoids and small cell lung cancers. The systematic measurement of these cytomorphonuclear parameters seems to define an objective, reproducible "scale" of differentiation that helps to define the atypical carcinoid and may be of value in establishing cytologic criteria for differential diagnosis.