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EN
Endotoxic shock is a major health threat caused by Gram-negative bacteria and their unique cell wall component, lipopolysaccharide which induces exaggerated production of proinflammatory cytokines. Although macrophages play a central role in the pathogenesis of endotoxic shock, NK1+ cells are also involved in this mechanism. NK1+ cells comprise two major populations, namely NK cells and NKT cells. It remains, however, elusive whether either NK cells, NKT cells or both are involved in induction of endotoxic shock. This review will focus on the relative contribution of these NK1+ cells to the pathogenesis of endotoxic shock.
EN
Initiation and propagation of the immune response is the result of a series of coordinated cellular and biochemical interactions that lead to the activation of multiple cell types. It is now clear that an optimal immune response requires a precise and rapid communication between different cell subsets. This phenomenon, referred to as cross-talk, is believed to be an essential component of the immune response that provides necessary inflammatory mediators and cytolytic activity for controlling infections and diseases. An example of an effective cooperation between different cell types has been recently illustrated by the finding that specific activation of CD1 restricted natural killer T cells (NK T) can quickly lead to the activation of other subsets of cells such as natural killer (NK) and CD8 T cells.
EN
NKT cells are the prominent manipulator in asthma development. Asthmatic NKT cells migrate from thymus, spleen, liver and bone marrow into blood vessels, and then concentrate in airway bronchi mucosa. This recruitment is dependent on high expression of CCR9 and engagement of CCL25/CCR9. NKT cells promote asthma in two different pathways. One is an indirect pathway. NKT cells contact with CD3+ T cells and induce them secreting large quantity of Th2 cytokines (IL-4, IL-13), which requires the participation of dentritic cells and the synergic signaling of CCL25/CCR9 and CD226. The other is a direct pathway. Circulating asthmatic NKT cells selectively highly express Th1 cytokines . Once reached airway epithelium, most NKT cells shift to Th2-bias, highly expressing IL-4, IL-13, but not IFN-alpha. Both pathways lead to airway hyperresponsiveness and inflammation, asthma development. Comparing to the well documented suppressive regulatory T cells, CD4+CD25+ T cells, NKT cells perform as a novel active regulator in asthma. These recent understanding of NKT cells performance in the development of asthma might unveil new therapy targets and management strategies for asthma.
EN
It is known that the liver is a major hematopoietic organ at fetal stages, but the hematopoiesis of this organ ceases of birth. However, the liver is still found to comprise c-kit+ stem cells and gives rise to extrathymic T cells, NK cells, and even granulocytes after birth. Extrathymic T cells generated in the liver of mice are identified as intermediate TCR (TCRint) cells, which include the NK1.1+TCRint (i.e. NKT cells) and NK1.1-TCRint subsets. Although extrathymic T cells are few in number during youth, they increase in number with advancing age. The number and function of extrathymic T cells are also elevated under conditions of stress, infections, malignancy, pregnancy, autoimmune disease, chronic GVH diseases, etc. Under these conditions, the mainstream of T cell differentiation in the thymus, which produces conventional T cells, is inversely suppressed. Extrathymic T cells comprise self-reactive forbidden clones and mediate cytotoxicity against abnormal self-cells. Therefore, they might be beneficial for the elimination of such cells. However, over-activation of extrathymic T cells might be responsible for the onset of certain autoimmune disease.
EN
This review summarizes the status of our knowledge on the structure, expression and function of CD1 proteins. An endosomal and non-endososomal pathways of CD1 antigen presentation are also described.
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