Selectively increased expression and functions of chemokine receptor CCR9 on CD4+ T cells from patients with T-cell lineage acute lymphocytic leukemia.
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.
Qiuping
Zhang
Z
Department of Immunology, Medical College, Wuhan University, Dong Hu Road 115, Wuchang 430 071, Wuhan, P.R. China.
Qun
Li
L
Chunsong
Hu
H
Xiaolian
Zhang
Z
Baojun
Huang
H
Mingzhen
Yang
Y
Chengming
Lao
L
Jinshen
He
H
Qingping
Gao
G
Kejian
Zhang
Z
Zhimin
Sun
S
Xuejun
Zhang
Z
Junyan
Liu
L
Jinquan
Tan
T
D000293:Adolescent; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007376:Interleukin-2 / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D054388:Receptors, CCR; D019707:Receptors, Chemokine / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D015854:Up-Regulation
C119309:CC chemokine receptor 9; D007376:Interleukin-2; D012333:RNA, Messenger; D054388:Receptors, CCR; D019707:Receptors, Chemokine; D015847:Interleukin-4