Hinrichs Anneline C, Blokland Sofie L M, Kruize Aike A, Lafeber Floris P J, Leavis Helen L, van Roon Joel A G
Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.
Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.
Front Immunol. 2022 Jun 1;13:887972. doi: 10.3389/fimmu.2022.887972. eCollection 2022.
Increased CCL5 expression and CD8 T cells have been shown to be pivotal regulators of immunopathology in primary Sjögren's syndrome (pSS) and pSS-like disease. Increased CCL5 expression by CCR9+ CD4 T cells has previously been implicated as a contributor to immunopathology in pSS. The role of CD8 T cells and in particular CCR9+ CD8 T cells and their potential to secrete CCL5 has not previously been studied in pSS. In this study we investigated both CCR9 and CCL5 expression by CD8 T cells in pSS patients compared to healthy controls (HC).
CCR9 expression on CD8 T cells from peripheral blood was compared between patients with pSS and HC by flow cytometry. Intracellular CCL5 expression by naive, memory and effector CCR9- and CCR9+ CD8 T cells was assessed. In addition, the capacity and pace of CCL5 release upon T cell activation was determined for all subsets and compared with CD4 T cells.
The frequency of circulating CCR9+ CD8 T cells in pSS patients is increased compared to HC. Antigen-experienced CD8 T cells, especially CCR9+ effector CD8 T cells, express the highest CCL5 levels, and release the highest levels of CCL5 upon activation. Memory and effector CD8 T cells of pSS patients express significantly less CCL5 and subsequently release less CCL5 upon stimulation compared to HC. CCR9+ CD8 T cells rapidly release CCL5 and significantly more than CCR9+ CD4 T cells.
CCR9+ CD8 T cells express more CCL5 than CCR9- CD8 T cells. CCL5 is rapidly released upon activation, resulting in reduced intracellular expression. Reduced CCL5 expression by an elevated number of antigen-experienced CCR9-expressing CD8 T cells in pSS patients points towards increased release . This suggests that CCL5 release by CCR9+ CD8 T cells contributes to immunopathology in pSS.
CCL5表达增加和CD8 T细胞已被证明是原发性干燥综合征（pSS）和pSS样疾病免疫病理的关键调节因子。此前，CCR9 + CD4 T细胞CCL5表达增加被认为是pSS免疫病理的一个促成因素。CD8 T细胞，尤其是CCR9 + CD8 T细胞的作用及其分泌CCL5的潜力在pSS中尚未得到研究。在本研究中，我们调查了pSS患者与健康对照（HC）相比，CD8 T细胞中CCR9和CCL5的表达情况。
通过流式细胞术比较pSS患者和HC外周血CD8 T细胞上CCR9的表达。评估幼稚、记忆和效应CCR9 - 和CCR9 + CD8 T细胞的细胞内CCL5表达。此外，测定所有亚群T细胞活化后CCL5释放的能力和速度，并与CD4 T细胞进行比较。
与HC相比，pSS患者循环CCR9 + CD8 T细胞的频率增加。抗原接触过的CD8 T细胞，尤其是CCR9 + 效应CD8 T细胞，表达最高水平的CCL5，并在激活后释放最高水平的CCL5。与HC相比，pSS患者的记忆和效应CD8 T细胞表达的CCL5明显较少，随后在刺激后释放的CCL5也较少。CCR9 + CD8 T细胞迅速释放CCL5，且明显多于CCR9 + CD4 T细胞。
CCR9 + CD8 T细胞比CCR9 - CD8 T细胞表达更多的CCL5。激活后CCL5迅速释放，导致细胞内表达减少。pSS患者中抗原接触过的表达CCR9的CD8 T细胞数量增加，CCL5表达减少，表明释放增加。这表明CCR9 + CD8 T细胞释放CCL5有助于pSS的免疫病理。
