Recruitment of T cells into bone marrow of ITP patients possibly due to elevated expression of VLA-4 and CX3CR1
pmid: 18519809
Recruitment of T cells into bone marrow of ITP patients possibly due to elevated expression of VLA-4 and CX3CR1
AbstractIn idiopathic thrombocytopenic purpura (ITP), platelets are destroyed in the spleen, liver, and bone marrow (BM) by autoantibodies and cytotoxic T cells. In a DNA microarray screen of peripheral blood T cells, we found that VLA-4, CX3CR1, and CXCR4, involved in T-cell homing, had increased expression in ITP patients compared with controls. However, we only found increased protein expression of VLA-4 on T cells from peripheral blood by flow cytometry. To address a possible recruitment of T cells into the organs involved in platelet destruction, we analyzed T cells in BM. In BM, T-cell surface expression of VLA-4 and CX3CR1 was increased in ITP patients compared with controls. Furthermore, the number of CD3+ T cells in BM, but not in blood, was increased in ITP patients compared with controls. This finding was confirmed by immunohistochemistry of BM biopsies. The number of regulatory T cells (CD4+/CD25bright) was decreased in the BM of ITP patients, whereas Fas expression was increased. In conclusion, ITP is associated with accumulation and activation of T cells in the BM. Recruitment of T cells into the target organ (eg, BM) is plausible and may be facilitated through increased VLA-4 and CX3CR1 expression. These molecules might serve as new treatment targets in ITP.
- University of Gothenburg Sweden
- Molecular Medicine Ireland Ireland
Adult, Male, Purpura, Thrombocytopenic, Idiopathic, Receptors, CXCR4, Adolescent, Gene Expression Profiling, T-Lymphocytes, CX3C Chemokine Receptor 1, Immunity, Integrin alpha4beta1, Middle Aged, Up-Regulation, Bone Marrow, Cell Movement, T-Lymphocyte Subsets, Humans, Female, Receptors, Chemokine, Aged
Adult, Male, Purpura, Thrombocytopenic, Idiopathic, Receptors, CXCR4, Adolescent, Gene Expression Profiling, T-Lymphocytes, CX3C Chemokine Receptor 1, Immunity, Integrin alpha4beta1, Middle Aged, Up-Regulation, Bone Marrow, Cell Movement, T-Lymphocyte Subsets, Humans, Female, Receptors, Chemokine, Aged
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