Development of reagents to study the turkey's immune response: cloning and characterisation of two turkey cytokines, interleukin (IL)-10 and IL-13.

The cDNAs of two turkey cytokines, interleukin (IL)-10 and IL-13, were cloned using oligonucleotide primers designed from their chicken orthologues. The coding regions of the chicken and turkey genes are highly conserved, with IL-10 and IL-13 exhibiting 94.1% and 90% nucleotide and 92% and 79.9% amino acid identity respectively. Both showed consistent mRNA expression in turkey lymphoid and gut tissues. Expression in non-lymphoid tissues was more variable but generally highest in the skin and trachea. Recombinant turkey IL-10 was expressed and bioactivity demonstrated by inhibition of IFN-γ synthesis from activated splenocytes. Chicken and turkey IL-10 cross-reacted in functional assays.

Tuberculin-specific T cells are reduced in active pulmonary tuberculosis compared to LTBI or status post BCG vaccination.

Functional characteristics of tuberculosis (TB)-specific CD4 T cells were studied in clinically active pulmonary TB (n = 21) and high TB exposure including LTBI (n = 17). Following tuberculin stimulation, activated CD4 T cells were identified by flow-cytometry (CD154 up-regulation, degranulation, interferon γ [IFN-γ], tumor necrosis factor α [TNF-α], and interleukin 2 [IL-2\ production). Interestingly, CD154 up-regulation accounted for ∼80% of activated CD4 T cells in the active TB group but just 40% in the controls, whereas IFN-γ accounted for only ∼50% of activated cells in each group. The frequencies of CD4 T cells displaying at least 1 activation marker discriminated better between the groups than those displaying degranulation or IFN-γ production alone.

The polo-like kinase inhibitor BI 2536 exhibits potent activity against malignant plasma cells and represents a novel therapy in multiple myeloma.

OBJECTIVE: Polo-like kinase 1 (Plk1) is a regulator of the cell cycle that has been implicated in the pathology of many cancers. We have investigated whether this kinase plays a role in multiple myeloma (MM) using the Plk1 inhibitor BI 2536. MATERIALS AND METHODS: We have used six MM cell lines and six patient-derived samples to determine the effects of the Plk1 inhibitor, BI 2536, on cell viability, apoptosis, and cytokinesis. We have also examined the effect of the microenvironment on these parameters and the effects of BI 2536 in combination with other antimyeloma agents. RESULTS: We show that MM cell lines and patient samples express PLK1 and that cell death by apoptosis occurs when Plk1 is inhibited. Cells treated with BI 2536 accumulate in the G(2)/M phase of the cell cycle causing endoduplication. The effects of BI 2536 are not abrogated when cells are cultured on extracellular matrix components, in the presence of interleukin-6, or with bone marrow stromal cells. CONCLUSIONS: Plk1 inhibition leads to cell death in MM cell lines and patient myeloma samples. Our data suggest that inhibition of Plk1 may have potential use as a therapeutic strategy in multiple myeloma.

Development of reagents to study the turkey's immune response: Identification and molecular cloning of turkey CD4, CD8alpha and CD28.

The cDNAs of three turkey CD markers, CD4, CD8alpha and CD28, were identified by screening a turkey cDNA library. The coding regions of the chicken and turkey genes are highly conserved, with 91.3-96.1% nucleotide (nt) and 84.2-95.5% amino acid (aa) identity. Identity was less conserved between avian CD markers and their mammalian homologues, ranging from 44.7 to 59.8% and 22.4 to 50.4% at the nt and aa levels, respectively. Anti-chicken CD8alpha and CD28 monoclonal antibodies were demonstrated to specifically cross-react with turkey CD8alpha and CD28, respectively.