More habitual physical activity is linked to the use of specific,more adaptive cognitive reappraisal strategies in dealing with stressful events

Physical activity may improve stress resilience and well‐being. However, specific links to individuals' coping abilities with stressful events are sparse. This study tested whether individuals reporting more physical activity in daily life showed a higher capacity for cognitive reappraisal in dealing with potential stressors. Ninety‐eight participants reported their regular physical activity in the Freiburger Questionnaire on Physical Activity and completed a maximum performance test of their inventiveness in generating reappraisals for situations depicting real‐life stressors. The latter provides scores for overall cognitive reappraisal capacity (quantity of ideas) and preference for specific cognitive reappraisal strategies (quality of ideas; positive reinterpretation; problem‐oriented, de‐emphasizing reappraisals). Additionally, participants' anxious and depressive dispositions and general creative abilities were assessed. Results showed no association between time spent on physical activities per week and total quantity of generated reappraisal ideas. However, a higher degree of physical activity was specifically linked to a greater relative preference for the reappraisal strategy of positive reinterpretation. Opposite associations emerged for the strategy of de‐emphasizing reappraisals. The findings support the notion of more adaptive cognitive reappraisal use in more physically active individuals and may advance research on interrelationships between physical activity and cognitive and affective functions implicated in stress management.     

Extracellular nucleotide signaling in solid organ transplantation

The role of extracellular purine nucleotides, including adenosine triphosphate (ATP) and adenosine, as modulators of posttransplantation outcome and ischemia‐reperfusion injury is becoming increasingly evident. Upon pathological release of ATP, binding and activation of P2 purinergic surface receptors promote tissue injury and inflammation, while the expression and activation of P1 receptors for adenosine have been shown to attenuate inflammation and limit ischemia‐induced damage, which are central to the viability and long‐term success of allografts. Here we review the current state of the transplant field with respect to the role of extracellular nucleotide signaling, with a focus on the sources and functions of extracellular ATP. The connection between ischemia reperfusion, purinergic signaling, and graft preservation, as well as the role of ATP and adenosine as driving factors in the promotion and suppression of posttransplant inflammation and allograft rejection, are discussed. We also examine novel therapeutic approaches that take advantage of the ischemia‐reperfusion‐responsive and immunomodulatory roles for purinergic signaling with the goal of enhancing graft viability, attenuating posttransplant inflammation, and minimizing complications including rejection, graft failure, and associated comorbidities.     

Radiation and host retinoic acid signaling promote the induction of gut‐homing donor T cells after allogeneic hematopoietic stem cell transplantation

Intestinal graft‐versus‐host disease (GVHD) remains a devastating complication after allogeneic hematopoietic stem cell transplantation (HSCT). Although it has been well established that gut‐tropic donor T cells expressing integrin α4β7 are required to cause intestinal damage, the factors that control the induction of this pathogenic T cell population remain to be identified. Retinoic acid (RA) plays an important role in inducing α4β7 expression on T cells. In this study, we showed that gene expression of retinaldehyde dehydrogenase, the key enzyme involved in RA biosynthesis, is significantly increased in the spleen and mesenteric lymph nodes (MLNs) of irradiated mice. In a C57BL/6‐into‐B6D2F1 allogeneic HSCT model, irradiation significantly increased the induction of α4β7⁺‐donor T cells in mesenteric lymph nodes and spleen. Furthermore, we found that the RA pathway modulates the ability of dendritic cells to imprint gut‐homing specificity on alloreactive T cells. We also showed that host dendritic cell RA signaling influences GVHD risk. Our studies identified radiation and recipient RA signaling as 2 primary factors that dictate the magnitude of gut‐homing donor T cell induction after allogeneic HSCT. Attenuating radiation‐associated inflammation and modulating host RA signaling represent feasible strategies to mitigate intestinal GVHD by reducing gut‐seeking pathogenic donor T cells.     

Memory T cell–mediated rejection is mitigated by FcγRIIB expression on CD8+ T cells

Donor‐reactive memory T cells generated via heterologous immunity represent a potent barrier to long‐term graft survival following transplantation because of their increased precursor frequency, rapid effector function, altered trafficking patterns, and reduced reliance on costimulation signals for activation. Thus, the identification of pathways that control memory T cell survival and secondary recall potential may provide new opportunities for therapeutic intervention. Here, we discovered that donor‐specific effector/memory CD8⁺ T cell populations generated via exposure to acute vs latent vs chronic infections contain differential frequencies of CD8⁺ T cells expressing the inhibitory Fc receptor FcγRIIB. Results indicated that frequencies of FcγRIIB‐expressing CD8⁺ donor‐reactive memory T cells inversely correlated with allograft rejection. Furthermore, adoptive T cell transfer of Fcgr2b^?/? CD8⁺ T cells resulted in an accumulation of donor‐specific CD8⁺ memory T cells and enhanced recall responses, indicating that FcγRIIB functions intrinsically to limit T cell CD8⁺ survival in vivo. Lastly, we show that deletion of FcγRIIB on donor‐specific CD8⁺ memory T cells precipitated costimulation blockade‐resistant rejection. These data therefore identify a novel cell‐intrinsic inhibitory pathway that functions to limit the risk of memory T cell–mediated rejection following transplantation and suggest that therapeutic manipulation of this pathway could improve outcomes in sensitized patients.     

Interleukin-10 Directly Inhibits CD8+ T Cell Function by Enhancing N-Glycan Branching to Decrease Antigen Sensitivity

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