Instituto Nacional de Enfermedades Respiratorias, Centro de Investigación en Enfermedades Infecciosas, México City, Mexico.
Instituto Nacional de Enfermedades Respiratorias, Centro de Investigación en Enfermedades Infecciosas, México City, Mexico.
Immunol Lett. 2021 Jul;235:22-31. doi: 10.1016/j.imlet.2021.04.004. Epub 2021 Apr 20.
The platelet endothelial cell adhesion molecule-1 (PECAM-1) or CD31 has been involved in regulation of T-cell tolerance, activation, survival and homing in mice cells. However, there is limited knowledge about the expression pattern and role of this molecule in human T cells, particularly in conditions of chronic immune activation.
We explored CD31 expression in T cell differentiation subsets of individuals with untreated HIV infection and in non-HIV-infected controls. We also assessed phenotypic differences between CD31+ and CD31- subsets in memory and terminally differentiated (TEMRA) CD4+ and CD8 + T cells.
Forty-one individuals with untreated HIV infection and 34 non-HIV-infected controls were included in the study. We compared the expression of CD31 in CD4+ and CD8 + T cells across stages of differentiation in the two study groups by flow cytometry. We also analyzed the expression of CD57 (a marker of senescence), Ki67 (a marker of cycling cells), PD-1 (a marker of exhaustion), and CD38/HLA-DR (a marker of immune activation) on memory and TEMRA CD31+ and CD31- T cells.
CD31 expression was significantly higher in CD8 + T cells than in CD4 + T cells, measured as frequency, absolute numbers and median fluorescence intensity (MFI), in both study groups (p < 0.0001 in all cases). Intermediate differentiation subsets of CD4+ and CD8 + T cells expressed higher levels of CD31 in the context of HIV infection (p < 0.001 in all cases). CD31 expression frequency decreased with cellular differentiation of CD4+ and CD8 + T cells in both groups, but this decrease was steeper in individuals without HIV infection (CD4+: p < 0.001 and CD8+: p < 0.0001). As expected, memory and TEMRA CD4+ and CD8 + T cells expressed significantly higher levels of CD57, PD-1, Ki67 and CD38/HLA-DR in HIV-infected compared to non-HIV-infected individuals (p < 0.01 in all cases). CD31 expression was associated with lower activation of memory (but not TEMRA) CD4 + T cells in non-HIV-infected persons, an effect not observed in the HIV-infected group. CD31 expression on memory CD8 + T cells of HIV-infected individuals was associated higher levels of PD-1 (p = 0.0019) and CD38/HLADR (p = 0.0345), and higher PD-1 expression on CD8 + TEMRA (p = 0.0024), an effect not observed in non-HIV-infected individuals.
In the context of HIV-associated chronic immune activation, specifically on memory CD8 + T cells, CD31 expression was associated with higher PD-1 and CD38/HLA-DR co-expression, suggesting that CD31 expression may result from an insufficient attempt to contain T cell exhaustion and activation. CD31-targeted therapies may contribute to modulate these cellular responses.
血小板内皮细胞黏附分子-1（PECAM-1）或 CD31 已被证明参与调节小鼠细胞中的 T 细胞耐受、激活、存活和归巢。然而，关于该分子在人类 T 细胞中的表达模式和作用的知识有限，特别是在慢性免疫激活的情况下。
我们研究了未经治疗的 HIV 感染个体和非 HIV 感染对照者的 T 细胞分化亚群中 CD31 的表达。我们还评估了记忆和终末分化（TEMRA）CD4+和 CD8+T 细胞中 CD31+和 CD31-亚群之间表型差异。
研究纳入了 41 名未经治疗的 HIV 感染者和 34 名非 HIV 感染者。我们通过流式细胞术比较了两组中 CD31 在 CD4+和 CD8+T 细胞分化阶段的表达。我们还分析了记忆和 TEMRA CD31+和 CD31-T 细胞上 CD57（衰老标志物）、Ki67（增殖细胞标志物）、PD-1（衰竭标志物）和 CD38/HLA-DR（免疫激活标志物）的表达。
在两组中，CD8+T 细胞中 CD31 的表达频率、绝对数量和中荧光强度（MFI）均显著高于 CD4+T 细胞（所有情况下均 p<0.0001）。HIV 感染时，CD4+和 CD8+T 细胞的中间分化亚群表达更高水平的 CD31（所有情况下均 p<0.001）。在两组中，CD4+和 CD8+T 细胞的 CD31 表达频率随着细胞分化而降低，但在未感染 HIV 的个体中下降更为明显（CD4+：p<0.001 和 CD8+：p<0.0001）。如预期的那样，与非 HIV 感染者相比，HIV 感染者的记忆和 TEMRA CD4+和 CD8+T 细胞表达更高水平的 CD57、PD-1、Ki67 和 CD38/HLA-DR（所有情况下均 p<0.01）。在非 HIV 感染者中，CD31 表达与记忆（但非 TEMRA）CD4+T 细胞的激活降低有关，而在 HIV 感染者中未观察到这种效应。HIV 感染者记忆 CD8+T 细胞上的 CD31 表达与更高水平的 PD-1（p=0.0019）和 CD38/HLADR（p=0.0345）以及更高的 CD8+TEMRA 上的 PD-1 表达相关（p=0.0024），而非 HIV 感染者则未观察到这种效应。
在 HIV 相关的慢性免疫激活背景下，特别是在记忆 CD8+T 细胞上，CD31 表达与更高水平的 PD-1 和 CD38/HLA-DR 共表达相关，表明 CD31 表达可能是由于试图控制 T 细胞衰竭和激活不足所致。CD31 靶向治疗可能有助于调节这些细胞反应。
