Activation by SLAM Family Receptors Contributes to NK Cell Mediated "Missing-Self" Recognition.

Natural Killer (NK) cells attack normal hematopoietic cells that do not express inhibitory MHC class I (MHC-I) molecules, but the ligands that activate NK cells remain incompletely defined. Here we show that the expression of the Signaling Lymphocyte Activation Molecule (SLAM) family members CD48 and Ly9 (CD229) by MHC-I-deficient tumor cells significantly contributes to NK cell activation. When NK cells develop in the presence of T cells or B cells that lack inhibitory MHC-I but express activating CD48 and Ly9 ligands, the NK cells' ability to respond to MHC-I-deficient tumor cells is severely compromised. In this situation, NK cells express normal levels of the corresponding activation receptors 2B4 (CD244) and Ly9 but these receptors are non-functional. This provides a partial explanation for the tolerance of NK cells to MHC-I-deficient cells in vivo. Activating signaling via 2B4 is restored when MHC-I-deficient T cells are removed, indicating that interactions with MHC-I-deficient T cells dominantly, but not permanently, impair the function of the 2B4 NK cell activation receptor. These data identify an important role of SLAM family receptors for NK cell mediated "missing-self" reactivity and suggest that NK cell tolerance in MHC-I mosaic mice is in part explained by an acquired dysfunction of SLAM family receptors

Document de consens per a la coinfecció pel Virus de la Immunodeficiència Humana i els Virus de les Hepatitis a Catalunya

VIH; Virus de les Hepatitis; CoinfeccióVIH; Virus de las Hepatitis; CoinfecciónHIV; Hepatitis virus; CoinfectionAquest manual ha estat preparat amb la intenció d'abordar els problemes que planteja el maneig de les persones malaltes amb coinfecció pel virus de la sida i els virus de l'hepatitis. A més, facilita als metges i metgesses assistencials els recursos necessaris per al diagnòstic i la presa de decisions terapèutiques, així com els criteris per ampliar la prevenció en tots aquells grups de població exposats a contraure aquestes infeccions.Este manual ha sido preparado con la intención de abordar los problemas que plantea el manejo de las personas enfermas con coinfección por el virus del sida y los virus de la hepatitis. Además, facilita a los médicos asistenciales los recursos necesarios para el diagnóstico y la toma de decisiones terapéuticas, así como los criterios para ampliar la prevención en todos aquellos grupos de población expuestos a contraer estas infecciones

CD69 Deficiency Enhances the Host Response to Vaccinia Virus Infection through Altered NK Cell Homeostasis.

During the host response to viral infection, the transmembrane CD69 protein is highly upregulated in all immune cells. We have studied the role of CD69 in the murine immune response to vaccinia virus (VACV) infection, and we report that the absence of CD69 enhances protection against VACV at both short and long times postinfection in immunocompetent and immunodeficient mice. Natural killer (NK) cells were implicated in the increased infection control, since the differences were greatly diminished when NK cells were depleted. This role of NK cells was not based on an altered NK cell reactivity, since CD69 did not affect the NK cell activation threshold in response to major histocompatibility complex class I NK cell targets or protein kinase C activation. Instead, NK cell numbers were increased in the spleen and peritoneum of CD69-deficient infected mice. That was not just secondary to better infection control in CD69-deficient mice, since NK cell numbers in the spleens and the blood of uninfected CD69(-/-) mice were already augmented. CD69-deficient NK cells from infected mice did not have an altered proliferation capacity. However, a lower spontaneous cell death rate was observed for CD69(-/-) lymphocytes. Thus, our results suggest that CD69 limits the innate immune response to VACV infection at least in part through cell homeostatic survival. We show that increased natural killer (NK) cell numbers augment the host response and survival after infection with vaccinia virus. This phenotype is found in the absence of CD69 in immunocompetent and immunodeficient hosts. As part of the innate immune system, NK lymphocytes are activated and participate in the defense against infection. Several studies have focused on the contribution of NK cells to protection against infection with vaccinia virus. In this study, it was demonstrated that the augmented early NK cell response in the absence of CD69 is responsible for the increased protection seen during infection with vaccinia virus even at late times of infection. This work indicates that the CD69 molecule may be a target of therapy to augment the response to poxvirus infection

Recommendations for Screening of Donor and Recipient Prior to Solid Organ Transplantation and to Minimize Transmission of Donor-Derived Infections.

In the context of solid organ transplantation, screening of recipients and organ donors is crucial, and should be performed with great rigour to minimize the reactivation or the risk of transmission of certain infectious processes. This review aims to update understanding of the possible pathologies involved, as well as of emerging infections that, as a result of globalization, are gaining increasing prominence on a daily basis