We confirmed that thymus NKT cells in humans were predominantly CD4+, but found that they were capable of significant cytokine production, including BGJ398 nmr IFN-γ, TNF and IL-4. Strong cytokine staining was also observed using NKT cells from cord blood,
illustrating that many CD4+ NKT cells in thymus and cord blood are functionally competent, although the pattern of cytokine expression was distinct from CD4+ NKT cells isolated from peripheral blood (Fig. 8). It also raises the question of whether or not there is a similar resident mature NKT cell population in the human thymus to that identified recently in mice [28]. We also performed the first analysis of NKT cells from human spleen. Fewer surface antigens were analysed for spleen NKT cells, but these appeared to be similarly heterogeneous in expression of cell surface antigens to blood-derived NKT cells, and were similar in their overall frequency and cytokine profile (IFN-γ, TNF and IL-4). This supports the analysis of blood NKT cells as a representative source of systemic NKT cells, at least relative to spleen, although more work is needed to confirm this, including comparative functional analysis of NKT cells from peripheral blood and from other peripheral tissues, such selleck inhibitor as liver and lymph nodes. Our data
clearly support the concept that heterogeneity within the NKT cell pool extends well beyond the CD4+ and CD4− subsets. More investigations are needed to define the functional diversity that exists within the human
NKT cell compartment and to correlate this with patterns of antigen expression and tissue residency, but it appears likely that that the diverse activities attributed to human NKT cells relies on an equally diverse array of subsets. The authors acknowledge the kind donation of tissue for research purposes by donors and their families. This research was supported by an NHMRC Project Grant (no. 454363) and an NHMRC Program Grant (no. 454569). S.P.B. was supported by an NHMRC Career Development Fellowship (no. 454731) and by the Australian Government Collaborative Research Network (CRN). S.P.B. is currently Methocarbamol supported as a Dorevitch Senior Research Fellow (at FECRI) and as a Robert H. T. Smith Fellow (Uni of Ballarat). D.I.G. is supported by an NHMRC Senior Principal Research Fellowship (no. 1020770). The authors declare no conflicts of interest. “
“The serine/threonine kinase LKB1 has a conserved role in Drosophila and nematodes to co-ordinate cell metabolism. During T lymphocyte development in the thymus, progenitors need to synchronize increased metabolism with the onset of proliferation and differentiation to ensure that they can meet the energy requirements for development.