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Blood, 15 August 2008, Vol. 112, No. 4, pp. 1078-1084.
Prepublished online as a Blood First Edition Paper on June 2, 2008; DOI 10.1182/blood-2008-02-139402.


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HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY

Recruitment of T cells into bone marrow of ITP patients possibly due to elevated expression of VLA-4 and CX3CR1

Bob Olsson1, Börje Ridell2, Lena Carlsson3, Stefan Jacobsson4, and Hans Wadenvik1

Departments of1 Internal Medicine, 2 Pathology, 3 Molecular and Clinical Medicine, and 4 Clinical Chemistry and Transfusion Medicine, the Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden

In 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.


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