Delayed acute allograft rejection in elderly recipients is associated with impaired effector/memory t-cell response

2010 ◽  
Vol 211 (3) ◽  
pp. S62
Author(s):  
Damanpreet Singh Bedi ◽  
Christian Denecke ◽  
Xupeng Ge ◽  
Irene K. Kim ◽  
Anke Jurisch ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Response ◽  
Allograft Rejection ◽  
T Cell Response ◽  
Effector Memory ◽  
Acute Allograft Rejection ◽  
Memory T Cell ◽  
Elderly Recipients

Impaired Effector/Memory CD8+ T Cell Response Delays Acute Allograft Rejection in Older Recipients

2012 ◽  
Vol 94 (10S) ◽  
pp. 1161
Author(s):  
A. Elkhal ◽  
D. S. Bedi ◽  
C. Denecke ◽  
A. Jurisch ◽  
I. Kim ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Response ◽  
Allograft Rejection ◽  
Cd8 T Cell ◽  
T Cell Response ◽  
Effector Memory ◽  
Acute Allograft Rejection ◽  
Memory Cd8 T Cell ◽  
Older Recipients

scholarly journals Children and adults with mild COVID-19 symptoms develop memory T cell immunity to SARS-CoV-2

2021 ◽  
Author(s):  
Patricia Kaaijk ◽  
Veronica Olivo Pimentel ◽  
Maarten E. Emmelot ◽  
Martien Poelen ◽  
Alper Cevirgel ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Response ◽  
T Cell Response ◽  
T Cell Immunity ◽  
Immune Memory ◽  
Effector Memory ◽  
Longitudinal Assessment ◽  
Memory T Cell ◽  
Cell Immunity

Background: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to considerable morbidity/mortality worldwide, but most infections, especially among children, have a mild course. However, it remains largely unknown whether infected children develop cellular immune memory. Methods: To determine whether a memory T cell response is being developed as an indicator for long-term immune protection, we performed a longitudinal assessment of the SARS-CoV-2-specific T cell response by IFN-γ ELISPOT and activation marker expression analyses of peripheral blood samples from children and adults with mild-to-moderate COVID-19. Results: Upon stimulation of PBMCs with heat-inactivated SARS-CoV-2 or overlapping peptides of spike (S-SARS-CoV-2) and nucleocapsid proteins, we found S-SARS-CoV-2-specific IFN-ɣ T cell responses in most infected children (83%) and all adults (100%) that were absent in unexposed controls. Frequencies of SARS-CoV-2-specific T cells were higher in infected adults, especially in those with moderate symptoms, compared to infected children. The S-SARS-CoV-2 IFN-ɣ T cell response correlated with S1-SARS-CoV-2-specific serum IgM, IgG, and IgA antibody concentrations. Predominantly, effector memory CD4+ T cells of a Th1 phenotype were activated upon exposure to SARS-CoV-2 antigens, which persisted for 4-8 weeks after symptom onset. We detected very low frequencies of SARS-CoV-2-reactive CD8+ T cells in these individuals. Conclusions: Our data indicate that an antigen-specific memory CD4+ T cell response is induced in children and adults with mild SARS-CoV-2 infection. T cell immunity induced after mild COVID-19 could contribute to protection against re-infection.

scholarly journals Modified Vaccinia Ankara–Vectored Vaccine Expressing Nucleoprotein and Matrix Protein 1 (M1) Activates Mucosal M1-Specific T-Cell Immunity and Tissue-Resident Memory T Cells in Human Nasopharynx-Associated Lymphoid Tissue

2019 ◽  
Vol 222 (5) ◽  
pp. 807-819 ◽  
Author(s):  
Suttida Puksuriwong ◽  
Muhammad S Ahmed ◽  
Ravi Sharma ◽  
Madhan Krishnan ◽  
Sam Leong ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Response ◽  
Lymphoid Tissue ◽  
Matrix Protein ◽  
T Cell Response ◽  
Effector Memory ◽  
Cell Phenotype ◽  
Memory T Cell ◽  
Cell Immunity

Abstract Background Increasing evidence supports a critical role of CD8+ T-cell immunity against influenza. Activation of mucosal CD8+ T cells, particularly tissue-resident memory T (TRM) cells recognizing conserved epitopes would mediate rapid and broad protection. Matrix protein 1 (M1) is a well-conserved internal protein. Methods We studied the capacity of modified vaccinia Ankara (MVA)–vectored vaccine expressing nucleoprotein (NP) and M1 (MVA-NP+M1) to activate M1-specific CD8+ T-cell response, including TRM cells, in nasopharynx-associated lymphoid tissue from children and adults. Results After MVA-NP+M1 stimulation, M1 was abundantly expressed in adenotonsillar epithelial cells and B cells. MVA-NP+M1 activated a marked interferon γ–secreting T-cell response to M1 peptides. Using tetramer staining, we showed the vaccine activated a marked increase in M158–66 peptide-specific CD8+ T cells in tonsillar mononuclear cells of HLA-matched individuals. We also demonstrated MVA-NP+M1 activated a substantial increase in TRM cells exhibiting effector memory T-cell phenotype. On recall antigen recognition, M1-specific T cells rapidly undergo cytotoxic degranulation, release granzyme B and proinflammatory cytokines, leading to target cell killing. Conclusions MVA-NP+M1 elicits a substantial M1-specific T-cell response, including TRM cells, in nasopharynx-associated lymphoid tissue, demonstrating its strong capacity to expand memory T-cell pool exhibiting effector memory T-cell phenotype, therefore offering great potential for rapid and broad protection against influenza reinfection.

scholarly journals Deciphering the state of immune silence in fatal COVID-19 patients

2020 ◽  
Author(s):  
Pierre Bost ◽  
Francesco De Sanctis ◽  
Stefania Cane ◽  
Stefano Ugel ◽  
Katia Donadello ◽  
...  
Keyword(s):  
T Cell ◽  
Clinical Outcome ◽  
Immune Suppression ◽  
Cell Response ◽  
T Cell Response ◽  
Lymphoid Cells ◽  
Effector Memory ◽  
Exact Nature ◽  
Memory T Cell ◽  
Arginase 1

Since the beginning of the SARS-CoV-2 pandemic, COVID-19 has appeared as a unique disease with unconventional tissue and systemic immune features. While COVID-19 severe forms share clinical and laboratory aspects with various pathologies such as hemophagocytic lymphohistiocytosis, sepsis or cytokine release syndrome, their exact nature remains unknown. This is severely impeding the ability to treat patients facing severe stages of the disease. To this aim, we performed an in-depth, single-cell RNA-seq analysis of more than 150.000 immune cells isolated from matched blood samples and broncho-alveolar lavage fluids of COVID-19 patients and healthy controls, and integrated it with clinical, immunological and functional ex vivo data. We unveiled an immune signature of disease severity that correlated with the accumulation of naive lymphoid cells in the lung and an expansion and activation of myeloid cells in the periphery. Moreover, we demonstrated that myeloid-driven immune suppression is a hallmark of COVID-19 evolution and arginase 1 expression is significantly associated with monocyte immune regulatory features. Noteworthy, we found monocyte and neutrophil immune suppression loss associated with fatal clinical outcome in severe pa-tients. Additionally, our analysis discovered that the strongest association of the patients clinical outcome and immune phenotype is the lung T cell response. We found that patients with a robust CXCR6+ effector memory T cell response have better outcomes. This result is line with the rs11385942 COVID-19 risk allel, which is in proximity to the CXCR6 gene and suggest effector memory T cell are a primary feature in COVID-19 patients. By systemically quantifying the viral landscape in the lung of severe patients, we indeed identified Herpes-Simplex-Virus 1 (HSV-1) as a potential opportunistic virus in COVID-19 patients. Lastly, we observed an unexpectedly high SARS-CoV-2 viral load in an immuno-compromised patient, allowing us to study the SARS-CoV-2 in-vivo life cycle. The development of myeloid dysfunctions and the impairment of lymphoid arm establish a condition of immune paralysis that supports secondary bacteria and virus infection and can progress to immune silence in patients facing death.

scholarly journals Kv1.3 channel blockade with the Vm24 scorpion toxin attenuates the CD4+ effector memory T cell response to TCR stimulation

2018 ◽  
Vol 16 (1) ◽  
Author(s):  
José Ignacio Veytia-Bucheli ◽  
Juana María Jiménez-Vargas ◽  
Erika Isabel Melchy-Pérez ◽  
Monserrat Alba Sandoval-Hernández ◽  
Lourival Domingos Possani ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Response ◽  
T Cell Response ◽  
Scorpion Toxin ◽  
Effector Memory ◽  
Channel Blockade ◽  
Memory T Cell ◽  
Kv1.3 Channel

High-mobility group box 1 accelerates early acute allograft rejection via enhancing IL-17+γδ T-cell response

2014 ◽  
Vol 27 (4) ◽  
pp. 399-407 ◽  
Author(s):  
Quansong Xia ◽  
Lihua Duan ◽  
Lifeng Shi ◽  
Fang Zheng ◽  
Feili Gong ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Response ◽  
Allograft Rejection ◽  
High Mobility ◽  
T Cell Response ◽  
High Mobility Group ◽  
Γδ T Cell ◽  
Acute Allograft Rejection

scholarly journals Deciphering the state of immune silence in fatal COVID-19 patients

2020 ◽  
Author(s):  
Ido Amit ◽  
Pierre Bost ◽  
Francesco De Sanctis ◽  
Stefania Canè ◽  
Ugel Stefano ◽  
...  
Keyword(s):  
T Cell ◽  
Clinical Outcome ◽  
Immune Suppression ◽  
Cell Response ◽  
T Cell Response ◽  
Lymphoid Cells ◽  
Effector Memory ◽  
Exact Nature ◽  
Memory T Cell ◽  
Arginase 1

Abstract Since the beginning of the SARS-CoV-2 pandemic, COVID-19 has appeared as a unique disease with unconventional tissue and systemic immune features. While COVID-19 severe forms share clinical and laboratory aspects with various pathologies such as hemophagocytic lymphohistiocyto-sis, sepsis or cytokine release syndrome, their exact nature remains unknown. This is severely imped-ing the ability to treat patients facing severe stages of the disease. To this aim, we performed an in-depth, single-cell RNA-seq analysis of more than 150.000 immune cells isolated from matched blood samples and broncho-alveolar lavage fluids of COVID-19 patients and healthy controls, and integrated it with clinical, immunological and functional ex vivo data. We unveiled an immune sig-nature of disease severity that correlated with the accumulation of naïve lymphoid cells in the lung and an expansion and activation of myeloid cells in the periphery. Moreover, we demonstrated that myeloid-driven immune suppression is a hallmark of COVID-19 evolution and arginase 1 expression is significantly associated with monocyte immune regulatory features. Noteworthy, we found mon-ocyte and neutrophil immune suppression loss associated with fatal clinical outcome in severe pa-tients. Additionally, our analysis discovered that the strongest association of the patients clinical outcome and immune phenotype is the lung T cell response. We found that patients with a robust CXCR6+ effector memory T cell response have better outcomes. This result is line with the rs11385942 COVID-19 risk allel, which is in proximity to the CXCR6 gene and suggest effector memory T cell are a primary feature in COVID-19 patients. By systemically quantifying the viral landscape in the lung of severe patients, we indeed identified Herpes-Simplex-Virus 1 (HSV-1) as a potential opportunistic virus in COVID-19 patients. Lastly, we observed an unexpectedly high SARS-CoV-2 viral load in an immuno-compromised patient, allowing us to study the SARS-CoV-2 in-vivo life cycle. The development of myeloid dysfunctions and the impairment of lymphoid arm establish a condition of immune paralysis that supports secondary bacteria and virus infection and can progress to “immune silence” in patients facing death.

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