Modulation of calcitonin secretion by modification of calcium channels?

Voltage-dependent calcium channels (VDCC) regulating Ca++ influx through the cellular plasma membrane play a major role in the Ca(++)-induced calcitonin (CT) secretion. Using rat C-cells (rMTC 6-23 cell line), we have studied the effect of repetitive stimulation by either Ca++ (2 mM) or glucagon (10 microM) or epinephrine (10 microM) on CT secretion. Following a Ca(++)-induced initial rise, CT release declined to basal levels after about four hours despite high Ca++; addition of 10 microM glucagon to the "Ca++ desensitized C-cells" yielded the normal stimulatory effect of glucagon on CT release. Repetitive stimulation with glucagon showed a constant stimulatory action over an eight-hour period. In contrast, repetitive stimulation with 10 microM epinephrine caused an initial rise followed by a gradual decline of CT release over six hours. The observed desensitization of Ca(++)-induced CT secretion may be due to a modification of VDCC in C-cells. Whether or not the desensitization of epinephrine-induced CT release occurs independently of the regulation of VDCC remains unclear.     

Long-term interleukin-10 presence induces the development of a novel, monocyte-derived cell type

Interleukin (IL)-10 is one of the most crucial immunoregulatory cytokines. Its short-term effects have been analysed extensively, but little is known about its long-term effects. This is of considerable importance, as high systemic IL-10 levels are present for long periods in patients with persistent viral infections, certain cancers and in critical care patients. Our study investigated the effects of the long-term presence of IL-10 on human peripheral blood monocytes. In vitro, IL-10 treatment of these cells for 7 days induced the development of a novel cell type characterized by unique phenotypical and functional characteristics. These cells showed high HLA-DR expression and low expression of CD86 and other co-stimulatory molecules on their surface. The mRNA levels of both HLA-DR and CD86 were high, but no intracellular accumulation of CD86 protein was observed. With respect to its function, these cells showed strongly diminished tumour necrosis factor-alpha production following lipopolysaccharide stimulation, strongly diminished allogenic CD4(+) T cell stimulatory capacity, and even induced a hyporesponsive state in CD4(+) T cells. The phenotype remained stable despite the removal of IL-10. In vivo, we found monocytic cells from patients exhibiting this phenotype after long-term IL-10 exposure. These results complement our knowledge further about the biological effects of IL-10 and may provide an explanation for the sustained immunodeficiency in cases of the persistent presence of systemic IL-10.     

CD45RA(bright)/CD11a(bright) CD8+ T cells: effector T cells [In Process Citation]

An important aspect of peripheral T cell development is the differentiation from naive into memory cells. To distinguish naive from memory cells, CD45RA and CD11a are commonly used: CD45RA+ or CD11a(dim) T cells are regarded as naive, while CD45RA- or CD11a(bright) T cells are thought to be of memory type. There is, however, a CD8+ T cell subset which is CD45RA+ and at the same time CD11a(bright). It increases with age and in patients with systemic viral infections, though its functional role in the immune response is unknown. In the present study, we give evidence that this subset is related to memory- like T cells as it produces IFN-gamma and tumor necrosis factor-alpha, contains high levels of perforin, and expresses CD95 in the same way as memory-type CD45RA-/CD11a(bright) CD8+ T cells. Since it contains a high percentage of CD28- and CD57+ cells, is increased in size and granularity, and is transiently expressed following in vitro stimulation of naive CD8+ T cells, we speculate that this subset mainly represents recently activated effector T cells that are able to interact with CD80 and CD86 (B7-1 and B7-2 respectively) negative tissue cells.