Sex- and age-specific clinical and immunological features of coronavirus disease 2019

To simultaneously determine clinical and immunological responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in young and old females and males, 681 coronavirus disease 2019 (COVID-19) patients and 369 normal controls (NCs) were analyzed based on age and sex classifications using multiple linear regression analysis. Compared to the age-matched NCs, both young and old male and female non-comorbid COVID-19 patients had lower lymphocyte counts and alanine aminotransferase (ALT) concentration, and only young male and female patients had lower neutrophil counts. Compared to young patients, both old males and females had significantly higher plasma ALT and AST concentrations. Compared to young and old females, age-matched males had higher plasma ALT and AST concentrations, but only young males had higher C-reactive protein (CRP) concentration. Compared to females, old males, but not young males, showed higher incidence of critical illness. Compared to young patients, old females had more leukocyte and neutrophil counts above the normal upper limit and B cell count below the normal lower limit (NLL), while old males had more lymphocyte and natural killer (NK) cell counts below the NLL. No sex or age associations with B cell and NK cell counts were observed. However, there were age-dependent decreases in CD8⁺ T-cell counts in both male and female COVID-19 patients. Age was negatively associated with CD8⁺ T cell counts but positively associated with neutrophil count, CRP, ALT, and AST concentrations, and sex (females) was negatively associated with neutrophil count, CRP, ALT, and AST concentrations. The present study suggests that SARS-CoV-2 infection mainly induced 1) beneficial sex (female)-related differences regarding reduced COVID-19 disease severity and negative associations with inflammatory responses and liver damage, and 2) harmful age-related differences relating to negative associations with CD8⁺ T cell count and positive associations with inflammatory responses and liver damage. Thus, sex and age are biological variables that should be considered in the prevention and treatment of COVID-19.     

Phenotypes and Functions of SARS-CoV-2-Reactive T Cells

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), which is an ongoing pandemic disease. SARS-CoV-2-specific CD4⁺ and CD8⁺ T-cell responses have been detected and characterized not only in COVID-19 patients and convalescents, but also unexposed individuals. Here, we review the phenotypes and functions of SARS-CoV-2-specific T cells in COVID-19 patients and the relationships between SARS-CoV-2-specific T-cell responses and COVID-19 severity. In addition, we describe the phenotypes and functions of SARS-CoV-2-specific memory T cells after recovery from COVID-19 and discuss the presence of SARS-CoV-2-reactive T cells in unexposed individuals and SARS-CoV-2-specific T-cell responses elicited by COVID-19 vaccines. A better understanding of T-cell responses is important for effective control of the current COVID-19 pandemic.     

Prolonged humoral and cellular immunity in COVID-19-recovered patients

By the beginning of 2021, the battle against coronavirus disease 2019 (COVID-19) remains ongoing. Investigating the adaptive immune response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19, in patients who have recovered from this disease could contribute to our understanding of the natural host immune response. We enrolled 38 participants in this study. 7 healthy participants and 31 COVID-19 patients who had recovered from COVID-19 and categorized them into 3 groups according to their previous clinical presentations: 10 moderate, 9 mild, and 12 asymptomatic. Flow cytometry analysis of peripheral lymphocyte counts in recovered patients showed significantly increased levels of CD4⁺ T cells in patients with a history of mild and moderate COVID-19 symptoms compared with those healthy individuals (p < 0.05 and p < 0.0001 respectively). whereas no significant difference was observed in the CD8⁺ T cell percentage in COVID-19-recovered patients compared with healthy individuals. Our study demonstrated that antibodies against the SARS-CoV-2 spike protein (anti-S) IgG antibody production could be observed in all recovered COVID-19 patients, regardless of whether they were asymptomatic (p < 0.05)or presented with mild (p < 0.0001) or moderate symptoms (p < 0.01). Anti-S IgG antibodies could be detected in participants up to 90 days post-infection. In conclusion, the lymphocyte levels in recovered patients were associated with the clinical presentation of the disease, and further analysis is required to investigate relationships between different clinical presentations and lymphocyte activation and function.     

Dynamics of NK,CD8 and Tfh cell mediated the production of cytokines and antiviral antibodies in Chinese patients with moderate COVID‐19

Recent studies have demonstrated a marked decrease in peripheral lymphocyte levels in patients with coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Few studies have focused on the changes of NK, T‐ and B‐cell subsets, inflammatory cytokines and virus‐specific antibodies in patients with moderate COVID‐19. A total of 11 RT‐PCR‐confirmed convalescent patients with COVID‐19 and 11 patients with non‐SARS‐CoV‐2 pneumonia (control patients) were enrolled in this study. NK, CD8⁺ T, CD4⁺ T, Tfh‐like and B‐cell subsets were analysed using flow cytometry. Cytokines and SARS‐CoV‐2‐specific antibodies were analysed using an electrochemiluminescence immunoassay. NK cell counts were significantly higher in patients with COVID‐19 than in control patients (P = 0.017). Effector memory CD8⁺ T‐cell counts significantly increased in patients with COVID‐19 during a convalescent period of 1 week (P = 0.041). TIM‐3⁺ Tfh‐like cell and CD226⁺ Tfh‐like cell counts significantly increased (P = 0.027) and decreased (P = 0.022), respectively, during the same period. Moreover, ICOS⁺ Tfh‐like cell counts tended to decrease (P = 0.074). No abnormal increase in cytokine levels was observed. The high expression of NK cells is important in innate immune response against SARS‐CoV‐2. The increase in effector memory CD8⁺ T‐cell counts, the up‐regulation of inhibitory molecules and the down‐regulation of active molecules on CD4⁺ T cells and Tfh‐like cells in patients with COVID‐19 would benefit the maintenance of balanced cellular and humoural immune responses, may prevent the development of severe cases and contribute to the recovery of patients with COVID‐19.     

Impaired function and delayed regeneration of dendritic cells in COVID-19

Disease manifestations in COVID-19 range from mild to severe illness associated with a dysregulated innate immune response. Alterations in function and regeneration of dendritic cells (DCs) and monocytes may contribute to immunopathology and influence adaptive immune responses in COVID-19 patients. We analyzed circulating DC and monocyte subsets in 65 hospitalized COVID-19 patients with mild/moderate or severe disease from acute illness to recovery and in healthy controls. Persisting reduction of all DC subpopulations was accompanied by an expansion of proliferating Lineage⁻HLADR⁺ cells lacking DC markers. Increased frequency of CD163⁺ CD14⁺ cells within the recently discovered DC3 subpopulation in patients with more severe disease was associated with systemic inflammation, activated T follicular helper cells, and antibody-secreting cells. Persistent downregulation of CD86 and upregulation of programmed death-ligand 1 (PD-L1) in conventional DCs (cDC2 and DC3) and classical monocytes associated with a reduced capacity to stimulate naïve CD4⁺ T cells correlated with disease severity. Long-lasting depletion and functional impairment of DCs and monocytes may have consequences for susceptibility to secondary infections and therapy of COVID-19 patients.     

Contributions of T Lymphocyte Abnormalities to Therapeutic Outcomes in Newly Diagnosed Patients with Immune Thrombocytopenia

T cell abnormalities have been reported to play an important role in pathogenesis of immune thrombocytopenia (ITP) besides specific autoantibodies towards platelet. The aim of this study was to explore the clinical importance of T lymphocyte subsets in adult patients with newly diagnosed ITP before and after first-line treatment. Elderly ITP patients were also studied and we tried to analyze the relationships between these items and therapeutic outcomes. The patients were treated with intravenous immunoglobulin (IVIG) plus corticosteroids and therapeutic responses were evaluated. As a result, compared with the controls, absolute lymphocyte counts in ITP patients decreased significantly before treatment. After treatment, lymphocyte counts restored to control level regardless of their treatment outcomes. In addition, we observed increased IgG and CD19⁺ cell expression and decreased CD4⁺/CD8⁺ cell ratio in both whole ITP group and elderly group before treatment. After treatment, the increased IgG and CD19⁺ cell expression could be reduced in both respond and non-respond group regardless of patient age, while CD4⁺/CD8⁺ cell ratio could not be corrected in non-respond ITP patients. In non-respond ITP patients, increased CD8⁺ cell expression was noticed and could not be corrected by first-line treatment. Furthermore, even lower NK cell expression was found in non-respond elderly patients after treatment when compared with that in controls. Our findings suggest that ITP patients usually had less numbers of peripheral lymphocytes and patients with higher levels of CD8⁺ cells or lower levels of CD4⁺/CD8⁺ cell ratio were less likely to respond to first-line treatment. Lower levels of NK cells made therapies in elderly ITP patients even more difficult.     

The Decrease of Peripheral Blood CD4+ T Cells Indicates Abdominal Compartment Syndrome in Severe Acute Pancreatitis

Objective

Few data are available on the role of T lymphocytes and inflammatory cytokines in abdominal compartment syndrome (ACS) in severe acute pancreatitis (SAP). We conducted a retrospective study to assess the risk factors associated with ACS in SAP.

Methods

A total of 76 SAP patients who were admitted within 24 hours after symptom onset in our study. There were 36 patients suffering from ACS and 40 from intra-abdominal hypertension (IAH). On the 1^st, 3^rd and 7^th days after hospital admission, the following variables were assessed: serum value of C-reactive protein (CRP), and the proportions of peripheral CD4⁺ and CD8⁺ T lymphocytes. Acute Physiology and Chronic Health Evaluation II (APACHE II) score, and computed tomography severity index (CTSI) score were assessed on days 1 and 7 after hospitalization.

Results

Compared with the patients with IAH, ACS patients showed statistically higher CRP value on 7^th day after hospital admission, proportions of CD4⁺ T cells on days 1, 3, 7 and CD4⁺ / CD8⁺ ratio on day 1 were significantly lower (P < 0.05, respectively). A CD4⁺ T cell proportion of 30.3% on the 1^st day indicated ACS with an area under the curve (AUC) of 0.774, a sensitivity with 82.5% and specificity with 72.0%, respectively. Sensitivity / specificity for predicting ACS in SAP patients on day 1 was 70.0% / 68.0% for CD4⁺ / CD8⁺ ratio, 72.2% / 65.0% for APACHE II score.

Conclusions

The reduction of peripheral blood CD4⁺ T lymphocytes is associated with ACS in SAP, and may act as a potential predictor of ACS in SAP.     

手足口病合并脑炎患儿外周血T淋巴细胞亚群、血清VCAM-1及CRP的表达水平及其检测价值分析

摘要 目的：探讨与分析手足口病（HFMD）合并脑炎患儿外周血T淋巴细胞亚群、血清VCAM-1及CRP的表达水平及其检测价值。方法：2017年4月到2020年10月选择在本院诊治的手足口病合并脑炎患儿42例作为合并组,同期选择手足口病不合并脑炎患儿68例作为对照组,检测两组外周血T淋巴细胞亚群、血清血管细胞粘附分子-1（VCAM-）及C-反应蛋白（CRP）表达水平,并判断检测价值与进行相关性分析。结果：合并组的CD4⁺、CD8⁺T淋巴细胞相对比例都明显少于对照组（P<0.05）。合并组的血清VCAM-1及CRP含量明显高于对照组（P<0.05）。在80例患儿中,Spearsman分析显示CD4⁺、CD8⁺T淋巴细胞相对比例和血清VCAM-1、CRP含量都与手足口病合并脑炎的发生存在相关性（P<0.05）。二分类Logistic回归分析显示CD4⁺、CD8⁺T淋巴细胞相对比例和血清VCAM-1、CRP含量都为导致手足口病合并脑炎发生的重要因素（P<0.05）。结论：手足口病合并脑炎患儿多伴随有外周血T淋巴细胞亚群异常与血清VCAM-1、CRP的高表达,CD4⁺、CD8⁺T淋巴细胞相对比例、血清VCAM-1、CRP含量都为导致手足口病合并脑炎发生的重要因素。     

Analysis of peripheral blood lymphocyte subsets and prognosis in patients with septic shock

The purpose of the study is to study the relationship between peripheral blood lymphocyte subset proportion and prognosis in patients with septic shock. Fifty‐two patients with septic shock, admitted to the intensive care unit between March 2007 and December 2010, were enrolled in this study. Peripheral blood lymphocyte subset proportions were measured using flow cytometry. The percentage of CD3⁺CD4⁺ T lymphocytes and CD19⁺ lymphocytes, CD4⁺/CD8⁺ T cell ratio were substantially lower in patients with septic shock compared to the control group (P < 0.01). The percentage of CD3⁺CD8⁺ T lymphocytes did not differ significantly between the two groups (P > 0.05). The percentage of CD16⁺CD56⁺ lymphocytes was higher in patients with septic shock than in the control group (P < 0.01). Compared with the survivor group, the percentage of CD3⁺CD4⁺ T lymphocytes and CD19⁺ lymphocytes, CD4⁺/CD8⁺ T cell ratio were clearly lower in the non‐survivor group (P < 0.01). There was no difference in the percentage of CD3⁺CD8⁺ T lymphocytes between the non‐survivor and survivor groups (P > 0.05). The percentage of CD16⁺CD56⁺ lymphocytes was higher in the non‐survivor group than in the survivor group (P < 0.05). The total maximum SOFA score and the delta SOFA score were much higher in the non‐survivor group than in the survivor group (P < 0.01). Immune imbalance occurs in patients with septic shock. Peripheral blood lymphocyte subset proportion and SOFA scores can be used to assess the treatment and prognosis of septic shock.     

慢阻肺患者运动负荷气道反应性与T细胞亚群的关系

摘要 目的：探讨与分析慢性阻塞性肺疾病（COPD）患者运动负荷气道反应性与T细胞亚群的关系。方法：2020年1月到2022年4月选择在本院诊治的慢阻肺患者88例作为慢阻肺组,同期选择在本院进行健康体检者88例作为健康组,检测两组T细胞亚群含量,判定两组的运动负荷气道反应性情况并进行相关性分析。结果：慢阻肺组的CD8⁺T淋巴细胞比例明显高于健康组,CD3⁺T淋巴细胞、CD4⁺T淋巴细胞比例明显低于健康组（P<0.05）。慢阻肺组的运动负荷气道反应性发生率为20.9 %,明显高于健康组的1.2 %（P<0.05）。在慢阻肺中,Spearsman分析显示运动负荷气道反应性发生率与CD3+T淋巴细胞、CD4⁺T淋巴细胞、CD8⁺T淋巴细胞比例存在相关性（P<0.05）。logistic回归分析显示CD3⁺T淋巴细胞、CD4⁺T淋巴细胞、CD8⁺T淋巴细胞比例都为影响运动负荷气道反应性发生的重要危险因素（P<0.05）。结论：慢阻肺患者多伴随有T细胞亚群异常,也多伴随有运动负荷气道反应性,运动负荷气道反应性与T细胞亚群存在相关性,也表明T细胞亚群紊乱是导致运动负荷气道反应性发生的重要因素。     

Decreased regulatory T‐cells and CD4+/CD8+ ratio correlate with disease onset and progression in patients with generalized vitiligo

The aim of present study was to evaluate CD4⁺/CD8⁺ ratio and CD4⁺CD25^hiFoxP3⁺ Tregs in GV patients with reference to their effect on disease onset and progression. Flow cytometry was used for determination of CD4⁺/CD8⁺ ratio and Tregs in 82 patients and 50 controls. CD8⁺ T‐cell counts were significantly higher in GV patients as compared with controls (p = 0.003). Active GV patients showed higher CD8⁺ T‐cell counts compared with stable GV patients (p = 0.001). The CD4⁺/CD8⁺ ratio decreased significantly in patients as compared with controls (p = 0.001). Moreover, the ratio in active GV patients significantly lowered as compared with stable GV patients (p = 0.002). Significant decrease in Treg cell percentage and counts in GV patients was observed compared with controls (p = 0.009, p = 0.008) with significant reduction in FoxP3 expression (p = 0.024). Treg cell percentage and counts were significantly decreased in active GV patients compared with stable GV patients (p = 0.007, p = 0.002). Our results suggest that an imbalance of CD4⁺/CD8⁺ ratio and natural Tregs in frequency and function might be involved in the T‐cell mediated pathogenesis of GV and its progression.     

Alteration of inhibitory and activating natural killer cell receptor expression on T cells in human immunodeficiency virus-infected Chinese

T cell expression of NKRs can trigger or inhibit cell‐mediated cytotoxicity. However, few studies on T lymphocyte NKR expression in HIV infection exist. Here, we examined the expression patterns of NKG2D, NKG2A, and KIR3DL1 on CD8⁺ and CD3⁺CD8^? cells by multicolor flow cytometry in groups of patients with HIV, AIDS or HAART‐treated AIDS, as well as HIV‐negative normal controls. Individual analysis of KIR3DL1 on CD3⁺CD8⁺ or CD3⁺CD8^? cells revealed no significant differences among any of the groups (P > 0.05). In contrast, the percentage of NKG2A⁺NKG2D^?CD8⁺ T cells was higher in the AIDS group than in the HIV‐negative normal control group (P < 0.01). Meanwhile, the prevalence of NKG2D⁺NKG2A^?CD8⁺T cells was lower in the AIDS group than in HIV‐negative normal controls (P < 0.001). Similar results were also observed for the percentage of NKG2A⁺NKG2D^? on CD3⁺CD8^?cells. However, in contrast to CD8⁺ T cells, the frequencies of NKG2D⁺NKG2A^? on CD3⁺CD8^? cells were higher in AIDS and HIV patients than in HIV‐negative normal controls (P < 0.01, P < 0.05, respectively). The percentage of NKG2A⁺NKG2D^?CD8⁺ T cells was negatively correlated with CD4⁺ T cell counts (r=?0.499, P < 0.01), while the percentage of NKG2D⁺NKG2A^?CD8⁺ T cells was positively correlated with CD4⁺ T cell counts (r= 0.494, P < 0.01). The percentage of NKG2D⁺NKG2A^?CD3⁺CD8^? T cells was also positively correlated with viral load (r= 0.527, P < 0.01) and negatively correlated with CD4⁺ T cell counts (r=?0.397, P < 0.05). Finally, HAART treatment reversed the changes in NKR expression caused by HIV infection. These results indicate that the expression of NKRs on T cells may be correlated with HIV disease progression.     

PD-1+ immune cell infiltration inversely correlates with survival of operable breast cancer patients

The programmed death-1 (PD-1) molecule is mainly expressed on functionally “exhausted” CD8⁺ T cells, dampening the host antitumor immune response. We evaluated the ratio between effective and regulatory T cells (Tregs) and PD-1 expression as a prognostic factor for operable breast cancer patients. A series of 218 newly diagnosed invasive breast cancer patients who had undergone primary surgery at Ruijin Hospital were identified. The influence of CD8⁺ cytotoxic T lymphocytes, FOXP3⁺ (Treg cell marker), and PD-1⁺ immune cell counts on prognosis was analyzed utilizing immunohistochemistry. Both PD-1⁺ immune cells and FOXP3⁺ Tregs counts were significantly associated with unfavorable prognostic factors. In bivariate, but not multivariate analysis, high tumor infiltrating PD-1⁺ cell counts correlated with significantly shorter patient survival. Our results suggest a prognostic value of the PD-1⁺ immune cell population in such breast cancer patients. Targeting the PD-1 pathway may be a feasible approach to treating patients with breast cancer.     

CD8<Superscript>+</Superscript> T cell expansion in HIV/HCV coinfection is associated with systemic inflammation

High prevalence of non-AIDS-defining illnesses in treated HIV-infected patients is associated with increased peripheral CD8⁺ T cell counts. Hepatitis C virus (HCV) coinfection is an additional risk factor for the development of non-AIDS events. We found that, in HIV/HCV coinfection, the increased proportion of CD8⁺ T lymphocytes is due to the effector memory and terminal effector T cells gain. Moreover, in these patients, the accumulation of highly differentiated forms of CD8⁺ T lymphocytes was associated with increased concentrations of inflammatory indices.     

Poor Immune Reconstitution in HIV-Infected Patients Associates with High Percentage of Regulatory CD4+ T Cells

CD4⁺ regulatory T cells (Tregs) are essential for the maintenance of the immune system''s equilibrium, by dampening the activation of potential auto-reactive T cells and avoiding excessive immune activation. To correctly perform their function, Tregs must be maintained at the right proportion with respect to effector T cells. Since this equilibrium is frequently disrupted in individuals infected with the human immunodeficiency virus (HIV), we hypothesize that its deregulation could hamper immune reconstitution in patients with poor CD4⁺ T cell recovery under highly active antiretroviral therapy (HAART). We analysed Tregs percentages amongst CD4⁺ T cells in 53 HIV-infected patients under HAART, with suppression of viral replication and distinct levels of immune reconstitution. As controls, 51 healthy individuals were also analysed. We observed that amongst the patients with Nadir values (the lowest CD4⁺ T cell counts achieved) <200 cells/µL, the individuals with high Tregs percentages (≥10% of total CD4⁺ T cells) had the worse CD4⁺ T cell reconstitution. In accordance, the well-described direct correlation between the Nadir value and CD4⁺ T cell reconstitution is clearly more evident in individuals with high Tregs proportions. Furthermore, we observed a strong negative correlation between Tregs percentages and CD4⁺ T cell recovery among immunological non-responder HIV⁺ individuals. All together, this work shows that high Tregs frequency is an important factor associated with sub-optimal CD4⁺ T cell recovery. This is particularly relevant for immunological non-responders with low Nadir values. Our results suggest that the Tregs proportion might be of clinical relevance to define cut-offs for HAART initiation.     

The Elevated Secreted Immunoglobulin D Enhanced the Activation of Peripheral Blood Mononuclear Cells in Rheumatoid Arthritis

Immunoglobulin D (IgD) is a surface immunoglobulin that is expressed as either membrane IgD (mIgD) or secreted IgD (sIgD). Researchers have shown that sIgD is often elevated in patients with autoimmune diseases. The possible roles of sIgD on the function of peripheral blood mononuclear cells (PBMCs) in rheumatoid arthritis (RA) are still unclear. In this study, we compared the expression of sIgD, mIgD and IgD receptor (IgDR) in RA patients and healthy controls, and investigated the effect of sIgD on the function of PBMCs. We found that the levels of sIgD, mIgD and IgDR were significantly higher in RA patients compared with healthy controls. The concentrations of sIgD were positively correlated with soluble receptor activator of nuclear factor-κB ligand (sRANKL), rheumatoid factor (RF) and C-reactive protein (CRP) in RA patients. Strikingly, IgD could enhance the proliferation of PBMCs and induce IL-1α, IL-1β, TNF-α, IL-6 and IL-10 production from PBMCs. Moreover, the percentage of activated T cell subsets (CD4⁺CD69⁺, CD4⁺CD154⁺) and activated B cell subsets (CD19⁺CD23⁺, CD19⁺CD21⁺, CD19⁺IgD⁺ and CD19^-CD138⁺) were increased by IgD. The percentage of unactivated T cell subset (CD4⁺CD62L⁺) and immature B cell subset (CD19⁺IgM⁺IgD^-) were decreased by IgD in PBMCs. Furthermore, the expressions of IgDR on T and B cells were significantly increased by treatment with IgD. Our results demonstrate that IgD enhanced the activation of PBMCs, which may contribute to RA pathogenesis. Therefore, IgD could be a potential novel immunotherapeutic target for the management of RA.     

Skewed ratios between CD3(+) T cells and monocytes are associated with poor prognosis in patients with HBV-related acute-on-chronic liver failure

Tempering of the innate immune response by T lymphocytes has been demonstrated to play a critical role in protecting animals from inflammation-induced death; however, its role in humans remains unknown. Patients with HBV-related acute-on-chronic liver failure (ACLF) share a striking similarity to the inflammatory response in septic shock where a hyperactive innate response is observed. The present study attempted to characterize the features of CD3⁺ T cells and monocytes and evaluate their clinical implications in 55 patients with HBV-related ACLF, 30 patients with chronic hepatitis B (CHB) and 30 healthy controls (HC). We found that the ratio between circulating CD3⁺ T cells and monocytes (T/M) was decreased in ACLF patients, due to decreased CD3 counts and increased monocyte counts compared with CHB and HC subjects. We also found that the T/M ratios were decreased from the early to the intermediate stage and reached the lowest value at the late stage in ACLF patients. Analyses with clinical parameters revealed that T/M ratios were negatively correlated with the Model for End-Stage Liver Disease Score and direct bilirubin, and positively correlated with prothrombin activity. Moreover, increased T/M ratios were observed in patients with good prognosis, but not in patients with a poor outcome; and ACLF patients who received liver transplantation exhibited an increased T/M ratio. Importantly, we found that programmed death-1 receptor (PD-1) was drastically upregulated on both CD4⁺ T and CD8⁺ T cells in ACLF, which at least in part contributed to the T-cell loss in these patients. Mechanically, the in vitro co-culture assay revealed that both CD4⁺ T and CD8⁺ T cells, as well as regulatory T cells, could inhibit TNF-α secretion by monocytes. In addition, the TNF-α levels in ACLF serum were negatively correlated with T/M ratios. In conclusion, our study identified the novel potential role of T/M ratio in predicting disease progression and provided novel evidences for further studies of the immunopathogenesis in ACLF.     

IL-15 immunotherapy is a viable strategy for COVID-19

Coronavirus disease 2019 (COVID-19) is a pulmonary inflammatory disease induced by a newly recognized coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 infection was detected for the first time in the city of Wuhan in China and spread all over the world at the beginning of 2020. Several millions of people have been infected with SARS-CoV-2, and almost 382,867 human deaths worldwide have been reported so far. Notably, there has been no specific, clinically approved vaccine or anti-viral treatment strategy for COVID-19. Herein, we review COVID-19, the viral replication, and its effect on promoting pulmonary fibro-inflammation via immune cell-mediated cytokine storms in humans. Several clinical trials are currently ongoing for anti-viral drugs, vaccines, and neutralizing antibodies against COVID-19. Viral clearance is the result of effective innate and adaptive immune responses. The pivotal role of interleukin (IL)-15 in viral clearance involves maintaining the balance of induced inflammatory cytokines and the homeostatic responses of natural killer and CD8⁺ T cells. This review presents supporting evidence of the impact of IL-15 immunotherapy on COVID-19.     

Regulatory KIR+RA+ T cells accumulate with age and are highly activated during viral respiratory disease

Severe respiratory viral infectious diseases such as influenza and COVID‐19 especially affect the older population. This is partly ascribed to diminished CD8⁺ T‐cell responses a result of aging. The phenotypical diversity of the CD8⁺ T‐cell population has made it difficult to identify the impact of aging on CD8⁺ T‐cell subsets associated with diminished CD8⁺ T‐cell responses. Here we identify a novel human CD8⁺ T‐cell subset characterized by expression of Killer‐cell Immunoglobulin‐like Receptors (KIR⁺) and CD45RA (RA⁺). These KIR⁺RA⁺ T cells accumulated with age in the blood of healthy individuals (20–82 years of age, n = 50), expressed high levels of aging‐related markers of T‐cell regulation, and were functionally capable of suppressing proliferation of other CD8⁺ T cells. Moreover, KIR⁺RA⁺ T cells were a major T‐cell subset becoming activated in older adults suffering from an acute respiratory viral infection (n = 36), including coronavirus and influenza virus infection. In addition, older adults with influenza A infection showed that higher activation status of their KIR⁺RA⁺ T cells associated with longer duration of respiratory symptoms. Together, our data indicate that KIR⁺RA⁺ T cells are a unique human T‐cell subset with regulatory properties that may explain susceptibility to viral respiratory disease at old age.