Expression of peripheral CD100 and its regulation to T lymphocytes function in patients with hepatocellular carcinoma

Huijuan FAN; Chun SONG

doi:10.3969/j.issn.1001-5256.2023.01.019

Volume 39 Issue 1

Jan. 2023

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Article Navigation > Journal of Clinical Hepatology > 2023 > 39(1): 128-136

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Expression of peripheral CD100 and its regulation to T lymphocytes function in patients with hepatocellular carcinoma

DOI: 10.3969/j.issn.1001-5256.2023.01.019

Huijuan FAN,
Chun SONG^{,
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Department of Gastroenterology, The Second Affiliated Hospital to Air force Military Medical University, Xi'an 710038, China

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Corresponding author: SONG Chun, 7902818098@qq.com (ORCID: 0000-0001-7896-1571)
Received Date: 2022-06-19
Accepted Date: 2022-07-22
Published Date: 2023-01-20

Abstract

Abstract

Objective To investigate the changes of peripheral CD100 in patients with hepatocellular carcinoma (HCC), and to assess the regulatory function of CD100 to T lymphocytes in HCC patients. Methods A prospective study was conducted. Fifty-seven HCC patients and twenty-two controls who were hospitalized in our hospital between April 2020 and July 2021 were enrolled. Anti-coagulant peripheral blood was collected. Plasma and peripheral blood mononuclear cells (PBMC) were isolated. Plasma soluble CD100 (sCD100) level was measured by enzyme-linked immunosorbent assay. Membrane-bound CD100 (mCD100) expression on CD4⁺ and CD8⁺ T lymphocytes was measured by flow cytometry. PBMC from HCC patients were stimulated with recombinant human CD100. Cellular proliferation was measured by cell counting kit-8. Different types of T helper cells (Th cells) and cytotoxic T cells (Tc cells) were assessed by flow cytometry. Perforin and granzyme B secretion by alpha fetoprotein (AFP) specific CD8⁺ T lymphocytes was assessed by enzyme-linked immunospot assay. CD8⁺ T lymphocytes were purified from HCC patients, and were stimulated with recombinant human CD100. Stimulated CD8⁺ T lymphocytes were co-cultured with HepG2 cells. AFP specific CD8⁺ T lymphocytes-induced HepG2 cell death was investigated. Student's t test or paired t test was used for comparison of normally distributed continuous data between two groups. Mann-Whitney U test was used for comparison of abnormally distributed continuous data between two groups. Chi square test was used for comparison of categorial data between two groups. Results Plasma sCD100 level was lower in HCC group when compared with control group ((2.73±0.58)ng/mL vs(3.33±0.84)ng/mL, t=3.584, P < 0.001). HCC group had higher percentage of mCD100⁺ cells (55.57%±11.33% vs 43.67%±6.40%, t=4.636, P < 0.001) and elevated mCD100 mean fluorescent intensity (MFI) (294.80±74.01 vs 255.00±74.01, t=2.126, P=0.037) within CD4⁺ T lymphocytes when compared with control group. Similarly, HCC group also had higher percentage of mCD100+ cells (48.65%±7.71% vs 41.74%±4.77%, t=3.914, P < 0.001) and elevated mCD100 MFI (289.20±89.30 vs 246.10±60.73, t=2.082, P=0.041) within CD8⁺ T lymphocytes when compared with control group. There were no significant differences of either cellular proliferation or T lymphocytes percentage between PBMC with and without recombinant human CD100 stimulation in HCC patients (all P > 0.05). The percentages of CD4⁺IFNγ⁺Th1 cells, CD4⁺IL-17A⁺Th17 cells, CD4⁺IL-22⁺Th22 cells, and CD8⁺IFNγ⁺Tc1 cells were notably increased in response to CD100 stimulation when compared with no CD100 stimulation (t=2.608、5.663、4.113、4605, all P < 0.05). There were no remarkably differences of either CD8⁺IL-17A⁺Tc17 or CD8⁺IL-22⁺Tc22 cell frequency between PBMCs with and without recombinant human CD100 stimulation in HCC patients (all P > 0.05). Perforin and granzyme B secretion by AFP specific CD8⁺ T lymphocytes were significantly elevated in response to CD100 stimulation when compared with no CD100 stimulation in HLA-A02 restricted HCC patients (P < 0.05). AFP specific CD8⁺ T lymphocytes-induced HepG2 cell death was also increased in response to CD100 stimulation (t=6.794、2.308, both P < 0.05). Conclusion There was an imbalance between sCD100 and mCD100 on T lymphocytes in HCC patients. Reduced sCD100 level might be insufficient for maintenance of T lymphocytes activity, leading to the immunotolerance in HCC.
- Liver Neoplasms,
- CD100,
- T-Lymphocytes

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Expression of peripheral CD100 and its regulation to T lymphocytes function in patients with hepatocellular carcinoma

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Expression of peripheral CD100 and its regulation to T lymphocytes function in patients with hepatocellular carcinoma

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