tetano
Editor, Senior Moderator
Front Immunol
. 2021 Sep 9;12:735125.
doi: 10.3389/fimmu.2021.735125. eCollection 2021.
Persistent High Percentage of HLA-DR [SUP]+[/SUP] CD38 [SUP]high[/SUP] CD8 [SUP]+[/SUP] T Cells Associated With Immune Disorder and Disease Severity of COVID-19
Juan Du[SUP] 1 [/SUP], Lirong Wei[SUP] 2 [/SUP], Guoli Li[SUP] 1 [/SUP], Mingxi Hua[SUP] 1 [/SUP], Yao Sun[SUP] 3 [/SUP], Di Wang[SUP] 4 [/SUP], Kai Han[SUP] 1 [/SUP], Yonghong Yan[SUP] 1 [/SUP], Chuan Song[SUP] 1 [/SUP], Rui Song[SUP] 2 [/SUP], Henghui Zhang[SUP] 1 [/SUP], Junyan Han[SUP] 1 [/SUP], Jingyuan Liu[SUP] 3 [/SUP], Yaxian Kong[SUP] 1 [/SUP]
Affiliations
Abstract
Background: The global outbreak of coronavirus disease 2019 (COVID-19) has turned into a worldwide public health crisis and caused more than 100,000,000 severe cases. Progressive lymphopenia, especially in T cells, was a prominent clinical feature of severe COVID-19. Activated HLA-DR[SUP]+[/SUP]CD38[SUP]+[/SUP] CD8[SUP]+[/SUP] T cells were enriched over a prolonged period from the lymphopenia patients who died from Ebola and influenza infection and in severe patients infected with SARS-CoV-2. However, the CD38[SUP]+[/SUP]HLA-DR[SUP]+[/SUP] CD8[SUP]+[/SUP] T population was reported to play contradictory roles in SARS-CoV-2 infection.
Methods: A total of 42 COVID-19 patients, including 32 mild or moderate and 10 severe or critical cases, who received care at Beijing Ditan Hospital were recruited into this retrospective study. Blood samples were first collected within 3 days of the hospital admission and once every 3-7 days during hospitalization. The longitudinal flow cytometric data were examined during hospitalization. Moreover, we evaluated serum levels of 45 cytokines/chemokines/growth factors and 14 soluble checkpoints using Luminex multiplex assay longitudinally.
Results: We revealed that the HLA-DR[SUP]+[/SUP]CD38[SUP]+[/SUP] CD8[SUP]+[/SUP] T population was heterogeneous, and could be divided into two subsets with distinct characteristics: HLA-DR[SUP]+[/SUP]CD38[SUP]dim[/SUP] and HLA-DR[SUP]+[/SUP]CD38[SUP]hi[/SUP]. We observed a persistent accumulation of HLA-DR[SUP]+[/SUP]CD38hi CD8[SUP]+[/SUP] T cells in severe COVID-19 patients. These HLA-DR[SUP]+[/SUP]CD38[SUP]hi[/SUP] CD8[SUP]+[/SUP] T cells were in a state of overactivation and consequent dysregulation manifested by expression of multiple inhibitory and stimulatory checkpoints, higher apoptotic sensitivity, impaired killing potential, and more exhausted transcriptional regulation compared to HLA-DR[SUP]+[/SUP]CD38[SUP]dim[/SUP] CD8[SUP]+[/SUP] T cells. Moreover, the clinical and laboratory data supported that only HLA-DR[SUP]+[/SUP]CD38[SUP]hi[/SUP] CD8[SUP]+[/SUP] T cells were associated with systemic inflammation, tissue injury, and immune disorders of severe COVID-19 patients.
Conclusions: Our findings indicated that HLA-DR[SUP]+[/SUP]CD38[SUP]hi[/SUP] CD8[SUP]+[/SUP] T cells were correlated with disease severity of COVID-19 rather than HLA-DR[SUP]+[/SUP]CD38[SUP]dim[/SUP] population.
Keywords: CD38; COVID-19; HLA-DR; immune disorder; severity.
. 2021 Sep 9;12:735125.
doi: 10.3389/fimmu.2021.735125. eCollection 2021.
Persistent High Percentage of HLA-DR [SUP]+[/SUP] CD38 [SUP]high[/SUP] CD8 [SUP]+[/SUP] T Cells Associated With Immune Disorder and Disease Severity of COVID-19
Juan Du[SUP] 1 [/SUP], Lirong Wei[SUP] 2 [/SUP], Guoli Li[SUP] 1 [/SUP], Mingxi Hua[SUP] 1 [/SUP], Yao Sun[SUP] 3 [/SUP], Di Wang[SUP] 4 [/SUP], Kai Han[SUP] 1 [/SUP], Yonghong Yan[SUP] 1 [/SUP], Chuan Song[SUP] 1 [/SUP], Rui Song[SUP] 2 [/SUP], Henghui Zhang[SUP] 1 [/SUP], Junyan Han[SUP] 1 [/SUP], Jingyuan Liu[SUP] 3 [/SUP], Yaxian Kong[SUP] 1 [/SUP]
Affiliations
- PMID: 34567001
- PMCID: PMC8458852
- DOI: 10.3389/fimmu.2021.735125
Abstract
Background: The global outbreak of coronavirus disease 2019 (COVID-19) has turned into a worldwide public health crisis and caused more than 100,000,000 severe cases. Progressive lymphopenia, especially in T cells, was a prominent clinical feature of severe COVID-19. Activated HLA-DR[SUP]+[/SUP]CD38[SUP]+[/SUP] CD8[SUP]+[/SUP] T cells were enriched over a prolonged period from the lymphopenia patients who died from Ebola and influenza infection and in severe patients infected with SARS-CoV-2. However, the CD38[SUP]+[/SUP]HLA-DR[SUP]+[/SUP] CD8[SUP]+[/SUP] T population was reported to play contradictory roles in SARS-CoV-2 infection.
Methods: A total of 42 COVID-19 patients, including 32 mild or moderate and 10 severe or critical cases, who received care at Beijing Ditan Hospital were recruited into this retrospective study. Blood samples were first collected within 3 days of the hospital admission and once every 3-7 days during hospitalization. The longitudinal flow cytometric data were examined during hospitalization. Moreover, we evaluated serum levels of 45 cytokines/chemokines/growth factors and 14 soluble checkpoints using Luminex multiplex assay longitudinally.
Results: We revealed that the HLA-DR[SUP]+[/SUP]CD38[SUP]+[/SUP] CD8[SUP]+[/SUP] T population was heterogeneous, and could be divided into two subsets with distinct characteristics: HLA-DR[SUP]+[/SUP]CD38[SUP]dim[/SUP] and HLA-DR[SUP]+[/SUP]CD38[SUP]hi[/SUP]. We observed a persistent accumulation of HLA-DR[SUP]+[/SUP]CD38hi CD8[SUP]+[/SUP] T cells in severe COVID-19 patients. These HLA-DR[SUP]+[/SUP]CD38[SUP]hi[/SUP] CD8[SUP]+[/SUP] T cells were in a state of overactivation and consequent dysregulation manifested by expression of multiple inhibitory and stimulatory checkpoints, higher apoptotic sensitivity, impaired killing potential, and more exhausted transcriptional regulation compared to HLA-DR[SUP]+[/SUP]CD38[SUP]dim[/SUP] CD8[SUP]+[/SUP] T cells. Moreover, the clinical and laboratory data supported that only HLA-DR[SUP]+[/SUP]CD38[SUP]hi[/SUP] CD8[SUP]+[/SUP] T cells were associated with systemic inflammation, tissue injury, and immune disorders of severe COVID-19 patients.
Conclusions: Our findings indicated that HLA-DR[SUP]+[/SUP]CD38[SUP]hi[/SUP] CD8[SUP]+[/SUP] T cells were correlated with disease severity of COVID-19 rather than HLA-DR[SUP]+[/SUP]CD38[SUP]dim[/SUP] population.
Keywords: CD38; COVID-19; HLA-DR; immune disorder; severity.