We demonstrate that interleukin‐10 (IL‐10) can inhibit T‐cell apoptosis. T cells, within a PBMC (peripheral blood mononuclear cell) population, were stimulated via the T‐cell receptor and grown in the presence of IL‐2. These cells had less apoptosis when in the continuous presence of IL‐10, compared with cells grown in the absence of IL–10. Conversely, when stimulated and grown in the presence of neutralizing antibody to IL‐10, there was an increase in T‐cell apoptosis. The in vitro rescue from apoptotic cell death of other lymphoid cells, such as germinal centre B cells, has been shown by others to involve a Bcl‐2 pathway. We therefore investigated whether IL‐10 might affect the Bcl‐2 expression on cultured T cells. By Western blotting we demonstrated that continuous exposure of IL‐10 to T cells (within a PBMC population) enhanced the expression of Bcl‐2. Furthermore, T cells protected from apoptotic cell death by IL‐10 were indistinguishable from viable untreated cells in their ability to proliferate to either immobilized anti‐CD3 or IL‐2. Thus, we have shown that continuous culture of T cells in the presence of IL‐10 will inhibit T‐cell apoptosis because of, at least in part, the upregulation of Bcl‐2, and this is associated with a normal proliferative function.

Objective. To characterize the cytokine profile of the activated T cell population derived from the synovial membrane of rheumatoid arthritis (RA) patients. Methods. Interleukin‐2 (IL‐2) was used to select for in vivo–activated T cells from the synovial membrane of 2 patients with RA, and the cells were cloned nonspecifically. The cytokine production profile of these clones was compared with that of clones derived from peripheral blood monocytes (PBM) by stimulating all clones for 24 hours with immobilized anti‐CD3 (coated at 10 μg/ml) or phorbol‐12‐myristate‐13‐acetate (10 ng/ml) plus soluble anti‐CD3 (1 μg/ml). Interferon‐γ (IFNγ), IL‐4, and IL‐10, the cytokines that discriminate between Th1 and Th2 cells and are involved in immunoregulation, were assayed by enzyme‐linked immunosorbent assay. Results. There was a difference in the cytokines produced by the clones derived from the rheumatoid membranes compared with clones derived from the periphery. Clones derived from both membranes and PBM were mostly IFNγ‐producers, i.e., either a Th0 or a Th1 profile. There was a high proportion of IFNγ/high IL‐10‐producing cells derived from the joint, but not from the periphery. Of clones derived from the synovial membrane of each of 2 RA patients, 100% and 50% produced both 1–10 ng/ml IFNγ and >7 ng/ml IL‐10, compared with <7% of clones derived from normal or RA peripheral blood. In addition, when autologous membrane and PBM were compared, the mean concentration of IL‐10 produced by the clones derived from the synovial membrane sample was significantly different from those produced by clones derived from peripheral blood (P < 0.02). Conclusion. The cytokine profile of the T cell clones that were obtained from the RA joint after expansion with IL‐2 is distinct from that of the T cells that are predominant in PBM. This supports the concept that the T cell subsets that accumulate in the joint are not a random sample. The high level of IL‐10 production by clones derived from the synovium suggests that this cytokine may be a major contributor to the endogenous immunosuppression that occurs in RA.

This retrospective study describes 35 dogs with non-resectable, grade I-III mast cell tumours on the head or limb treated with prednisolone (40 mg m(-2) daily) for 10-14 days prior to radiotherapy (4 x 800 cGy fractions at 7-day intervals) from a 4 MV linear accelerator. Prednisolone was continued at a reduced dose rate (20 mg m(-2)) during radiotherapy and for 2 months or longer afterwards. Eighteen of 24 tumours (75%) decreased in size in response to prednisolone treatment. By 6-8 weeks following radiotherapy, 12 dogs had achieved a complete remission and 19 a partial response. Two tumours remained static and two progressed during the course of treatment. The overall response rate was 88.5%. With long-term follow-up, 11 dogs experienced local recurrence (n = 4), metastasis (n = 5) or both (n = 2). The median progression-free interval was 1031 days (95% CI 277.44-1784.56, Kaplan-Meier), with 1- and 2-year progression-free rates of 60 and 52%, respectively. Tumour grade did not predict the prognosis for this group of dogs, but tumour location did affect the outcome. Dogs with tumours located on the limb survived longer than those with tumours on the head. The combination of prednisolone with radiotherapy appears to have a useful role in the management of measurable mast cell tumours sited on the head and distal extremities.