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Selectively Increased Expression and Functions of Chemokine Receptor CCR9 on CD4⁺ T Cells from Patients with T-Cell Lineage Acute Lymphocytic Leukemia¹

Department of Immunology, Medical College [Z. Q., Z. Xi., L. J., T. J.], and Department of Hematology, The First and Second Affiliated University Hospital [G. Q., Z. K.], Wuhan University, 430071 Wuhan; Department of Immunology, College of Basic Medical Sciences, Anhui Medical University, 230032 Hefei [L. Q., H. C., H. B., L. C., H. J., Z. Xu., T. J.]; Department of Hematology, The Affiliated University Hospital, Anhui Medical University, 230031 Hefei [Y. M.]; and Department of Hematology, The Provincial Hospital of Anhui, 230020 Hefei [S. Z.], Peoples Republic of China

In a total of 38 typical T-cell lineage acute lymphocytic leukemia (T-ALL) and T-cell lineage chronic lymphocytic leukemia (T-CLL) cases investigated, we found that CC chemokine receptor CCR9 was selectively and frequently expressed on T-ALL CD4⁺ T cells, was moderately expressed on T-CLL CD4⁺ T cells, and was rarely expressed on normal CD4⁺ T cells. These findings were demonstrated at protein and mRNA levels using flow cytometry and real-time quantitative reverse transcription-PCR technique and were verified by digital confocal microscopy and Northern blotting. Thymus-expressed chemokine, a ligand for CCR9, selectively induced T-ALL CD4⁺ T-cell chemotaxis and adhesion. Interleukin (IL)-2 and IL-4, together, down-regulated the expression and functions of CCR9 in T-ALL CD4⁺ T cells including chemotaxis and adhesion. It was also demonstrated that IL-2 and IL-4, together, internalized CCR9 on T-ALL CD4⁺ T cells and subsequently inhibited functions of CCR9 in these cells. Thymus-expressed chemokine mRNA was highly expressed in CD4⁺ T cells, involving lymph node and skin in T-ALL patients, and was expressed at moderate levels in lymph node and skin tissues in T-CLL patients. Our findings may provide new clues to understanding various aspects of T-ALL CD4⁺ T cells, such as functional expression of CCR9-thymus-expressed chemokine receptor-ligand pairs as well as the effects of IL-2 and IL-4, which may be especially important in cytokine/chemokine environment for the pathophysiological events of T-ALL CD4⁺ T-cell trafficking.

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