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Identification of a novel mycobacterial transcriptional regulator and its involvement in growth rate dependence and stringent control

FEMS Microbiology Letters, 2002, Vol.209(2), pp.261-266 [Peer Reviewed Journal]

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  • Title:
    Identification of a novel mycobacterial transcriptional regulator and its involvement in growth rate dependence and stringent control
  • Author: Kamalakannan, V ; Ramachandran, Geetha ; Narayanan, Sujatha ; Vasan, S.K ; Narayanan, P.R
  • Found In: FEMS Microbiology Letters, 2002, Vol.209(2), pp.261-266 [Peer Reviewed Journal]
  • Subjects: Promoter ; Transcriptional Regulator ; Stringent Response ; Induction ; Biology
  • Language: English
  • Description: Studies in experimental animal models of human autoimmune diseases have revealed that CD4(+)CD25(+) T regulatory (Tr) cells are of thymic origin and have potentials in preventing auto-aggressive immunity. Myasthenia gravis (MG) is the best-characterized autoimmune disease. Changes in the thymus are found in a majority of patients with MG. Thymectomy has beneficial effects on the disease severity and course in a substantial proportion of MG patients. But the occurrence and characteristics of Tr cells have not yet been defined in MG. We determined the frequencies and properties of circulating CD4(+)CD25(+) versus CD4(+)CD25(-) cells in MG patients and healthy controls (HCs), with special focus on the effect of thymectomy on CD4(+)CD25(+) cells. CD4(+)CD25(high) cells comprise only about 2% of blood lymphocytes in both MG patients and HCs. Frequencies of CD4(+)CD25(high) cells were similar in MG patients irrespective of treatment with thymectomy. CD4(+)CD25(+) cells in both MG patients and HCs are mainly memory T cells and are activated to a greater extent than CD4(+)CD25(-) cells, as reflected by high levels of CD45RO and human leucocyte antigen (HLA)-DR-positive cells. In both MG patients and HCs, CD4(+)CD25(+) cells also contained a high proportion of CD95-expressing cells as possible evidence of apoptosis-proneness. Upon stimulation with anti-CD3/CD28 monoclonal antibodies, CD4(+)CD25(+) cells responded more vigorously than CD4(+)CD25(-) cells in MG, irrespective of treatment with thymectomy, as well as in HCs. Although CD4(+)CD25(-) cells are mainly naïve T cells, in non-thymectomized MG patients, they are activated to a greater extent as reflected by higher expression of HLA-DR and CD95 on the surface compared to HCs. The data thus show that there is no deficiency of CD4(+)CD25(+) cells in MG, nor is the proportion of CD4(+)CD25(+) cells influenced by thymectomy.
  • Identifier: ISSN: 0378-1097 ; E-ISSN: 1574-6968 ; DOI: 10.1016/S0378-1097(02)00550-5

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