Spatial distribution, kinetics, signaling and cytokine production during homeostasis driven proliferation of CD4+ T cells

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• 作者：Deepak Sharma ; S. Santosh Kumar ; Rahul Checker ; Rashmi Raghu ; Shazia Khanam ; Sunil Krishnan ; Krishna Balaji Sainis
• 关键词：NF-κ ; B ; IL-6 ; Plumbagin ; Lymphopenia ; Inflammation
• 刊名：Molecular Immunology
• 出版年：2009
• 出版时间：July 2009
• 年：2009
• 卷：46
• 期：11-12
• 页码：2403-2412
• 全文大小：1602 K

文摘

During recovery from lymphopenia, the naïve T-cells undergo homeostasis driven proliferation (HDP) and acquire a memory phenotype. The HDP of T-cells requires signals derived from T-cell-receptor, p56lck kinase, IL-7R and IL-15R. However, the role of other signaling molecules during HDP of CD4+ T-cells remains speculative. The differentiation of naïve T-cells into Th1/Th2/Th17 or Treg populations during HDP is not well understood. Present report describes the spatial and signaling characteristics of HDP of CD4+ T-cells and their cytokine profiles. The HDP of CD4+ T-cells was found to occur only in specific areas (T-cell zones) of secondary lymphoid organs of lymphopenic mice. The inhibitors of MEK and PKC and their combination with inhibitors of PI3kinase and mTOR suppressed mitogen induced T-cell proliferation without affecting their HDP. The CD4+ T-cells taken from reconstituted lymphopenic mice showed activation of proteins involved in NF-κB pathway, significantly higher production of pro-inflammatory cytokine IL-6, and lower production of IL-4 as compared to T-cells from normal mice. Plumbagin, a known NF-κB blocker inhibited survival as well as HDP of CD4+ T-cells and IL-6 production in activated T-cells. Our results demonstrate the essential role of NF-kappaB during HDP of T-cells.