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

Blood. 2008 Aug 15;112(4):1078-84. doi: 10.1182/blood-2008-02-139402. Epub 2008 Jun 2.

Abstract

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(+)/CD25(bright)) 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Bone Marrow / pathology*
  • CX3C Chemokine Receptor 1
  • Cell Movement*
  • Female
  • Gene Expression Profiling
  • Humans
  • Immunity
  • Integrin alpha4beta1 / genetics*
  • Male
  • Middle Aged
  • Purpura, Thrombocytopenic, Idiopathic / immunology*
  • Receptors, CXCR4 / genetics*
  • Receptors, Chemokine / genetics*
  • T-Lymphocyte Subsets
  • T-Lymphocytes / physiology*
  • Up-Regulation / genetics

Substances

  • CX3C Chemokine Receptor 1
  • CX3CR1 protein, human
  • CXCR4 protein, human
  • Integrin alpha4beta1
  • Receptors, CXCR4
  • Receptors, Chemokine