The newly characterised HLA-B*41:84 allele, found in a prospective liver transplant candidate.

HLA-B*41:84 has a single base substitution in exon 2, altering glutamic acid to glutamine'.

The novel HLA-DQA1*05:05:17:03 allele, identified in a potential organ donor.

HLA-DQA1*05:05:17:03 differs from HLA-DQA1*05:05:01:02 by a single base substitution in exon 1 and HLA-DQA1*05:05:17:01 within introns 1 and 2.

The novel HLA-C*06:372 allele, identified in a stem cell donor of an old order mennonite ethnicity.

HLA-C*06:372 differs from HLA-C*06:02:01:01 by a single substitution in exon 4.

CXCL10 contributes to p38-mediated apoptosis in primary T lymphocytes in vitro.

CXCL10 is part of the group of interferon-stimulated genes and it plays an important role during different viral infections by inducing cell activation, chemotaxis and lymphocyte priming toward the Th1 phenotype. In this study, we investigated in vitro the effects of CXCL10 in activated human primary T lymphocytes in terms of apoptosis or survival, and delineated the signaling pathways that are involved. CXCL10, in combination with IL-2 and/or IFNα, induces apoptosis in T lymphocytes. Moreover, CXCL10-induced activation of CXCR3 also triggers pro-survival signals that can be blocked by pertussis toxin. The analysis of the downstream signaling kinases shows that apoptosis is p38 MAPK-dependent and the pro-survival signals rely on the sustained activation of PI3K and the transient activation of Akt. On the other hand, the transient activation of p44/p42 ERK did not have an impact on T lymphocyte survival. We propose an immunological model in which CXCL10, together with other co-stimulating cytokines, participates in the activation of T lymphocytes, promotes survival and expansion of certain lymphocyte subsets, and induces chemotaxis toward the infected tissues. On the other hand, CXCL10 might contribute to the triggering of apoptosis in other subsets of T lymphocytes, including those lymphocytes that were transiently activated but later lacked the appropriate sets of specific co-stimulating signals to ensure their survival.

Endogenous antiviral mechanisms of RNA interference: a comparative biology perspective.

RNA interference (RNAi) is a natural process that occurs in many organisms ranging from plants to mammals. In this process, double-stranded RNA or hairpin RNA is cleaved by a RNaseIII-type enzyme called Dicer into small interfering RNA duplex. This then directs sequence-specific, homology-dependent, posttranscriptional gene silencing by binding to its complementary RNA and triggering its elimination through degradation or by inducing translational inhibition. In plants, worms, and insects, RNAi is a strong antiviral defense mechanism. Although, at present, it is unclear whether RNA silencing naturally restricts viral infection in vertebrates, there are signs that this is certainly the case. In a relatively short period, RNAi has progressed to become an important experimental tool both in vitro and in vivo for the analysis of gene function and target validation in mammalian systems. In addition, RNA silencing has subsequently been found to be involved in translational repression, transcriptional inhibition, and DNA degradation. In this article we review the literature in this field, which may open doors to the many uses to which this important technology is being put, including the potential of RNAi as a therapeutic strategy for gene regulation to modulate host-pathogen interactions.

Effects of antigen and recombinant porcine cytokines on pig dendritic cell cytokine expression in vitro.

To evaluate variables influencing in vitro immune response induction, pig monocyte-derived DCs (moDCs) were treated with putative type-1 and type-2 antigens (Ags, killed Mycobacterium tuberculosis (Mtb) and hen egg white lysozyme (HEWL)) and recombinant porcine cytokines (IL-6, IL-10, IL-12, IFN-gamma and TNF-alpha). Responses were measured as moDC cytokine mRNA expression. Treatment of moDCs with HEWL increased IL-13 but not IL-12, IFN-gamma or IL-10 mRNA, suggesting a DC2 phenotype. Addition of TNF-alpha, IFN-gamma or IL-12 to HEWL-treated moDCs increased IL-12p35 and reduced IL-13 mRNA; suggesting a DC1 phenotype. Mtb increased moDC IL-12p35, IFN-gamma and to a lesser extent IL-13 mRNA. This DC1 bias was enhanced by TNF-alpha, IFN-gamma or IL-12, which increased IL-12p35 and to a lesser extent IL-10 mRNA but reduced IL-13 mRNA. Addition of IL-10 to Mtb-pulsed moDCs reduced IL-12p35, IFN-gamma and IL-13, but increased IL-10 mRNA, suggesting diversion from DC1 to DC2. Thus porcine moDCs treated with Ag and/or cytokines alter moDC cytokine expression confirming their likely ability to initiate and steer acquired immune response.