Partial break in tolerance of NKG2A-/LIR-1- single KIR+ NK cells early in the course of HLA-matched, KIR-mismatched hematopoietic cell transplantation.

Natural killer (NK) cell subpopulations from 8 HLA-matched but killer cell immunoglobulin-like receptor (KIR)/HLA-ligand-mismatched patient-donor pairs were analyzed in the course of allogeneic hematopoietic stem cell transplantation (HCT). The patients' post-transplantation NKG2A-/LIR-1- NK cells, which expressed only inhibitory KIRs for which the patient had no HLA class I ligands, showed higher cytotoxic capacity than the NKG2A-/LIR-1- NK cells lacking any inhibitory KIRs that remained tolerant throughout the course of HCT. The NKG2A+ NK cell subpopulations displayed the highest levels of cytotoxic activation, which appeared to be significantly enhanced in comparison with that in allogeneic graft's donors. LIR-1- NK cells were much more frequent after HCT than LIR-1+ NK cells and LIR-1 expression on NKG2A+ or NKG2A- NK cells was associated with significantly lower cytotoxic activities. Thus NKG2A-/LIR-1- NK cells expressing only HLA-mismatched KIRs show a partial break in tolerance in the first year following HCT. The failure to exclude LIR-1+ cells within the NKG2A- NK cell subset in previous studies could explain the earlier conflicting results. Thus systemic immune activation in patients following HCT augments the GvL effect through both increasing overall NK cell activities and partially breaking tolerance of unlicensed NK cells.

The gastrointestinal system--an essential target organ of the athlete's health and physical performance.

An athlete's ability to reach maximum performance is a direct result of physical and muscular performance, muscular and systemic stress tolerance, control and regulation of immune function, and adaptation to physical stress. In this complex sense, the gastrointestinal (GI) tract is also part of the system that controls and regulates adaptation and regeneration of the athlete. A well-balanced GI immune system and an optimized immune competence may protect the athlete from harmful pathogens; it may also protect against dietary as well as inhaled antigens. However, under conditions of mechanical and biochemical stress, the integrity of the GI mucosal block, particularly the epithelial hood, can be damaged, leading to a pathological uptake of toxic or immunogenic substrates. This may occur in endurance athletes, since gut symptomatology, nausea, vomiting, pain, bloating, diarrhea, cramping, and bleeding can be observed in up to half of all participants in endurance events. In addition, composition of stool and fecal microflora in endurance athletes has shown that there may be a specific need for nutritional support for mucosal immunity in highly trained but chronically stressed athletes. Proper diet during training and competition is a significant factor in guarding against GI symptoms and exercise-induced gastrointestinal side effects that may compromise immune competence and physical performance. The present review presents some important suggestions on the possible role of the GI tract in human performance and stress tolerance, and offers new insights about the influence of food quality on the immune system of the gut.