Recruitment of T cells into bone marrow of ITP patients possibly due to elevated expression of VLA-4 and CX3CR1.
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.
Departments ofInternal Medicine, the Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden. bob.olsson@medic.gu.se
Bob
B
Olsson
Börje
B
Ridell
Lena
L
Carlsson
Stefan
S
Jacobsson
Hans
H
Wadenvik
D000293:Adolescent; D000328:Adult; D000368:Aged; D001853:Bone Marrow / Q000473:pathology*; D000073883:CX3C Chemokine Receptor 1; D002465:Cell Movement; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007109:Immunity; D039041:Integrin alpha4beta1 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000276:immunology*; D019718:Receptors, CXCR4 / Q000235:genetics*; D019707:Receptors, Chemokine / Q000235:genetics*; D016176:T-Lymphocyte Subsets; D013601:T-Lymphocytes / Q000502:physiology*; D015854:Up-Regulation / Q000235:genetics
D000073883:CX3C Chemokine Receptor 1; C095235:CX3CR1 protein, human; C527276:CXCR4 protein, human; D039041:Integrin alpha4beta1; D019718:Receptors, CXCR4; D019707:Receptors, Chemokine