Espinar-Buitrago M S, Tarancon-Diez L, Vazquez-Alejo E, Magro-Lopez E, Genebat M, Romero-Candau F, Leal M, Muñoz-Fernandez M A
Immunology Section, Laboratorio Inmuno-Biología Molecular (LIBM), Hospital General Universitario Gregorio Marañón (HGUGM), Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), 28009, Madrid, Spain.
Centro de Investigación Biomédica en Red Bioingeniería, Biomateriales y Nanotecnología (CIBER-BBN), Madrid, Spain.
Immun Ageing. 2023 Jul 5;20(1):32. doi: 10.1186/s12979-023-00351-x.
Since the beginning of SARS-CoV2 pandemic, the mortality rate among elderly patients (60-90 years) has been around 50%, so age has been a determining factor of a worse COVID-19 prognosis. Associated with age, the thymic function involution and depletion plays an important role, that could be related to a dysregulated and ineffective innate and adaptive immune response against SARS-CoV2. Our study aims to further in vitro effect of human Thymosin-alpha-1 (α1Thy) treatment on the immune system in population groups with different thymic function levels in the scenario of SARS-CoV2 infection.
Activation markers such as CD40, CD80 and TIM-3 were upregulated in α1Thy presence, especially in plasmacytoid dendritic cells (pDCs) and, with increased TNFα production was observed compared to untreated condition. Co-cultures of CD4 + and CD8 + T cells with DCs treated with α1Thy in response to SARS-CoV2 peptides showed a decrease in the cytokine production compared to the condition without α1Thy pre-treated. A decrease in CD40L activation co-receptor expression in CD8 + LTs was also observed, as well as an increase in PD1 in CD4 + TLs expression in both age groups. In fact, there are no age-related differences in the immunomodulatory effect of the hormone, and it seems that effector memory and terminally differentiated memory T lymphocyte subsets were the most actively influenced by the immunomodulatory α1Thy effect. Finally, the polyfunctionality measured in SARS-CoV2 Specific-T cells response was maintained in α1Thy presence in total and memory subpopulations CD4 + and CD8 + T-cells, despite decreased proinflammatory cytokines production.
The hormone α1Thy could reduce, through the modulation of DCs, the amount of proinflammatory cytokines produced by T cells. Moreover, α1Thy improve lymphocyte functionality and could become a beneficial therapeutic alternative as an adjuvant in SARS-CoV2 treatment either in the acute phase after infection or reinfection. In addition, the effect on the T immune response means that α1Thy can be incorporated into the vaccination regimen, especially in the most immunologically vulnerable individuals such as the elderly.
Thymosin alpha 1, Dendritic cells, SARS-CoV2-specific T cells response, Immunomodulation.
自新冠病毒大流行开始以来，老年患者（60 - 90岁）的死亡率约为50%，因此年龄一直是新冠病毒感染预后较差的一个决定性因素。与年龄相关的胸腺功能衰退和耗竭起着重要作用，这可能与针对新冠病毒的先天免疫和适应性免疫反应失调及无效有关。我们的研究旨在进一步探讨在新冠病毒感染情况下，人胸腺肽α1（α1Thy）治疗对不同胸腺功能水平人群免疫系统的体外影响。
在α1Thy存在的情况下，诸如CD40、CD80和TIM - 3等激活标志物上调，尤其是在浆细胞样树突状细胞（pDCs）中，并且与未处理状态相比，观察到肿瘤坏死因子α（TNFα）产生增加。与未用α1Thy预处理的情况相比，用α1Thy处理的树突状细胞与新冠病毒肽反应时，CD4 + 和CD8 + T细胞的共培养显示细胞因子产生减少。在两个年龄组中，还观察到CD8 + 长寿命T细胞中CD40L激活共受体表达减少，以及CD4 + T细胞中PD1表达增加。事实上，该激素的免疫调节作用不存在年龄相关差异，并且似乎效应记忆和终末分化记忆T淋巴细胞亚群受免疫调节性α1Thy作用的影响最为活跃。最后，尽管促炎细胞因子产生减少，但在α1Thy存在的情况下，在总CD4 + 和CD8 + T细胞以及记忆亚群中，新冠病毒特异性T细胞反应中测量的多功能性得以维持。
激素α1Thy可通过调节树突状细胞来减少T细胞产生的促炎细胞因子数量。此外，α1Thy可改善淋巴细胞功能，并且在新冠病毒感染急性期或再次感染后作为辅助治疗可能成为一种有益的治疗选择。此外，对T免疫反应的影响意味着α1Thy可纳入疫苗接种方案，特别是在诸如老年人等免疫最脆弱的个体中。
胸腺肽α1、树突状细胞、新冠病毒特异性T细胞反应、免疫调节
