Identification of CCL1 as a Gene Differentially Expressed in CD4⁺T Cells Expressing TIM-3

Abstract

BackgroundT cell immunoglobulin mucin containing molecule (TIM)-3 is expressed in differentiated Th1 cells and is involved in the suppression of the cytokine production by these cells. However, the regulation of the expression of other T cell genes by TIM-3 is unclear. Herein, we attempted to identify differentially expressed genes in cells abundantly expressing TIM-3 compared to cells with low expression of TIM-3.MethodsTIM-3 overexpressing cell clones were established by transfection of Jurkat T cells with TIM-3 expression vector. For screening of differentially expressed genes, gene fishing technology based on reverse transcription-polymerase chain reaction (RT-PCR) using an annealing control primer system was used. The selected candidate genes were validated by semi quantitative and real-time RT-PCR.ResultsThe transcription of TIMP-1, IFITM1, PAR3 and CCL1 was different between TIM-3 overexpressing cells and control cells. However, only CCL1 transcription was significantly different in cells transiently transfected with TIM3 expression vector compared with control cells. CCL1 transcription was increased in primary human CD4+ T cells abundantly expressing TIM-3 but not in cells with low expression of TIM-3.ConclusionCCL1 was identified as a differentially transcribed gene in TIM-3-expressing CD4+ T cells.

TIM3 expression by leukemic and non‐leukemic myeloblasts

“…Several lines of evidence hint at this possibility. First, transcription of the Chemokine (C‐C motif) Ligand 1(CCL1) gene has been shown to be increased in a subset of human T cells abundantly expressing TIM3 as compared to cells with low TIM3 expression levels (12). Blockade of CCL1 inhibits T cell‐mediated suppressive function (13), and therefore, increased CCL1 could enhance T‐cell suppressive function and result in a reduced anti‐tumor response.…”

CEACAM1 structure and function in immunity and its therapeutic implications

“…Furthermore, reduced expression of CEACAM1 and TIM-3 on circulating CD4 + and CD8 + T lymphocytes in individuals with multiple sclerosis correlates with disinhibited T cell activation and consequently increased disease severity [132]. TIM-3 has been suggested to also possess activating functionality [133][134][135][136][137][138][139][140][141]. This raises the possibility that CEACAM1 associates with TIM-3 as it does other activating receptors and serves to inhibit its function or that CEACAM1 association with TIM-3 enables other novel inhibitory signaling mechanisms that remain to be determined.…”

The Possible Diagnostic and Prognostic Use of Systemic Chemokine Profiles in Clinical Medicine—The Experience in Acute Myeloid Leukemia from Disease Development and Diagnosis via Conventional Chemotherapy to Allogeneic Stem Cell Transplantation

“…Chemokines are small proteins (8–12 kDa) [1]; approximately 50 human chemokines and 20 receptors have been identified (Table 1) [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32], and they can be classified either on the basis of (i) the molecular structure, i.e. , the pattern of cysteine residues in the ligands or (ii) their functional characteristics, as inducible or inflammatory chemokines and constitutively expressed homeostatic chemokines [33].…”