scholarly journals Dynamics and turnover of memory CD8 T cell responses following yellow fever vaccination

2021 ◽  
Author(s):  
Veronika I. Zarnitsyna ◽  
Rama S. Akondy ◽  
Hasan Ahmed ◽  
Don J. McGuire ◽  
Vladimir G. Zarnitsyn ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Yellow Fever ◽  
Cd8 T Cells ◽  
Power Laws ◽  
First Year ◽  
Post Vaccination ◽  
Memory Cd8 T Cells ◽  
Cell Responses ◽  
Exponential Decline

AbstractUnderstanding how immunological memory lasts a lifetime requires quantifying changes in the number of memory cells as well as how their division and death rates change over time. We address these questions by using a statistically powerful mixed-effects differential equations framework to analyze data from two human studies that follow CD8 T cell responses to the yellow fever vaccine (YFV-17D). Models were first fit to the frequency and division rates of YFV-specific memory CD8 T cells 42 days to 1 year post-vaccination. A different dataset, on the loss of YFV-specific CD8 T cells over three decades, was used to assess out of sample predictions of our models. The commonly used exponential and bi-exponential decline models performed relatively poorly. Models with the cell loss following a power law (exactly or approximately) were most predictive. Notably, using only the first year of data, these models accurately predicted T cell frequencies up to 30 years post-vaccination. Our analyses suggest that division rates of these cells drop and plateau at a low level (0.001 per day, ~double estimates for naive T cells) within one year following vaccination, whereas death rates continue to decline for much longer. Our results show that power laws can be predictive for T cell memory, a finding that may be useful for vaccine evaluation and epidemiological modeling. Moreover, since power laws asymptotically decline more slowly than any exponential decline, our results help explain the longevity of immune memory phenomenologically.Author summaryImmunological memory, generated in response to infection or vaccination, may provide complete or partial protection from antigenically similar infections for the lifetime. Memory CD8 T cells are important players in protection from secondary viral infections but quantitative understanding of their dynamics in humans is limited. We analyze data from two studies where immunization with the yellow fever virus vaccine (YFV-17D) generates a mild acute infection and long-term memory. We find that: (i) the division rate of YFV-17D-specific CD8 T cells drops and stabilizes at ~ 0.1% per day during the first year following vaccination whereas the death rate declines more gradually, and (ii) the number of these cells declines approximately in accordance with a power law (∝time−0.82) for at least several decades following vaccination.

scholarly journals Dynamics and turnover of memory CD8 T cell responses following yellow fever vaccination

2021 ◽  
Vol 17 (10) ◽  
pp. e1009468
Author(s):  
Veronika I. Zarnitsyna ◽  
Rama S. Akondy ◽  
Hasan Ahmed ◽  
Donald J. McGuire ◽  
Vladimir G. Zarnitsyn ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Yellow Fever ◽  
Cd8 T Cells ◽  
Power Laws ◽  
Cd8 T Cell ◽  
Death Rates ◽  
Post Vaccination ◽  
Cell Responses ◽  
Exponential Decline

Understanding how immunological memory lasts a lifetime requires quantifying changes in the number of memory cells as well as how their division and death rates change over time. We address these questions by using a statistically powerful mixed-effects differential equations framework to analyze data from two human studies that follow CD8 T cell responses to the yellow fever vaccine (YFV-17D). Models were first fit to the frequency of YFV-specific memory CD8 T cells and deuterium enrichment in those cells 42 days to 1 year post-vaccination. A different dataset, on the loss of YFV-specific CD8 T cells over three decades, was used to assess out of sample predictions of our models. The commonly used exponential and bi-exponential decline models performed relatively poorly. Models with the cell loss following a power law (exactly or approximately) were most predictive. Notably, using only the first year of data, these models accurately predicted T cell frequencies up to 30 years post-vaccination. Our analyses suggest that division rates of these cells drop and plateau at a low level (0.1% per day, ∼ double the estimated values for naive T cells) within one year following vaccination, whereas death rates continue to decline for much longer. Our results show that power laws can be predictive for T cell memory, a finding that may be useful for vaccine evaluation and epidemiological modeling. Moreover, since power laws asymptotically decline more slowly than any exponential decline, our results help explain the longevity of immune memory phenomenologically.

Tissue-resident memory CD8+ T cells shape local and systemic secondary T cell responses

2020 ◽  
Vol 21 (9) ◽  
pp. 1070-1081 ◽  
Author(s):  
Felix M. Behr ◽  
Loreto Parga-Vidal ◽  
Natasja A. M. Kragten ◽  
Teunis J. P. van Dam ◽  
Thomas H. Wesselink ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
T Cell Responses ◽  
Memory Cd8 T Cells ◽  
Cell Responses

scholarly journals CD8 T Cells andToxoplasma gondii: A New Paradigm

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Jason P. Gigley ◽  
Rajarshi Bhadra ◽  
Imtiaz A. Khan
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Cd8 T Cell ◽  
Cytolytic Activity ◽  
New Paradigm ◽  
Memory Cd8 T Cells ◽  
Effector Cells ◽  
Cell Responses ◽  
Immune Pressure

CD8 T cells are essential for control ofToxoplasma gondiiinfection. Once activated they undergo differentiation into short-lived effector and memory precursor effector cells. As effector cells, CD8 T cells exert immune pressure on the parasite via production of inflammatory cytokines and through their cytolytic activity. Once immune control has been established, the parasite encysts and develops into chronic infection regulated by the memory CD8 T-cell population. Several signals are needed for this process to be initiated and for development of fully differentiated memory CD8 T cells. With newly developed tools including CD8 T-cell tetramers and TCR transgenic mice, dissecting the biology behindT. gondii-specific CD8 T-cell responses can now be more effectively addressed. In this paper, we discuss what is known about the signals required for effectiveT. gondii-specific CD8 T-cell development, their differentiation, and effector function.

NKp80 defines and stimulates a reactive subset of CD8 T cells

Blood ◽  
2009 ◽  
Vol 113 (2) ◽  
pp. 358-369 ◽  
Author(s):  
Sabrina Kuttruff ◽  
Sven Koch ◽  
Alexandra Kelp ◽  
Graham Pawelec ◽  
Hans-Georg Rammensee ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Natural Killer ◽  
Cd8 T Cells ◽  
Cell Subset ◽  
T Cell Responses ◽  
Effector Memory ◽  
Memory Cd8 T Cells ◽  
Cell Responses ◽  
Natural Killer Gene Complex

Abstract NKp80, an activating homodimeric C-type lectin-like receptor (CTLR), is expressed on essentially all human natural killer (NK) cells and stimulates their cytotoxicity and cytokine release. Recently, we demonstrated that the ligand for NKp80 is the myeloid-specific CTLR activation-induced C-type lectin (AICL), which is encoded in the natural killer gene complex (NKC) adjacent to NKp80. Here, we show that NKp80 also is expressed on a minor fraction of human CD8 T cells that exhibit a high responsiveness and an effector memory phenotype. Gene expression profiling and flow cytometric analyses revealed that this NKp80+ T-cell subset is characterized by the coexpression of other NK receptors and increased levels of cytotoxic effector molecules and adhesion molecules mediating access to sites of inflammation. NKp80 ligation augmented CD3-stimulated degranulation and interferon (IFN)γ secretion by effector memory T cells. Furthermore, engagement of NKp80 by AICL-expressing transfectants or macrophages markedly enhanced CD8 T-cell responses in alloreactive settings. Collectively, our data demonstrate that NKp80 is expressed on a highly responsive subset of effector memory CD8 T cells with an inflammatory NK-like phenotype and promotes T-cell responses toward AICL-expressing cells. Hence, NKp80 may enable effector memory CD8 T cells to interact functionally with cells of myeloid origin at sites of inflammation.

scholarly journals Age-Related Decline in Primary CD8+ T Cell Responses Is Associated with the Development of Senescence in Virtual Memory CD8+ T Cells

Cell Reports ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3512-3524 ◽  
Author(s):  
Kylie M. Quinn ◽  
Annette Fox ◽  
Kim L. Harland ◽  
Brendan E. Russ ◽  
Jasmine Li ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
T Cell Responses ◽  
Virtual Memory ◽  
Cd8 T Cell ◽  
Memory Cd8 T Cells ◽  
Cell Responses ◽  
Age Related

scholarly journals IL-2/Anti-IL-2 Antibody Complex Enhances Vaccine-Mediated Antigen-Specific CD8+T Cell Responses and Increases the Ratio of Effector/Memory CD8+T Cells to Regulatory T Cells

2008 ◽  
Vol 180 (7) ◽  
pp. 5118-5129 ◽  
Author(s):  
Sven Mostböck ◽  
M. E. Christine Lutsiak ◽  
Diane E. Milenic ◽  
Kwamena Baidoo ◽  
Jeffrey Schlom ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Cd8 T Cells ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Effector Memory ◽  
Memory Cd8 T Cells ◽  
Cell Responses ◽  
Antibody Complex

scholarly journals CCR2 Regulates Vaccine-Induced Mucosal T cell Memory to Influenza A Virus

2021 ◽  
Author(s):  
M Suresh ◽  
Woojong Lee ◽  
Brock Kingstad-Bakke ◽  
Ross Kedl ◽  
Yoshihiro Kawaoka
Keyword(s):  
T Cells ◽  
T Cell ◽  
Influenza A Virus ◽  
Cd8 T Cells ◽  
Protective Immunity ◽  
Influenza A ◽  
T Cell Responses ◽  
Viral Pathogens ◽  
Memory Cd8 T Cells ◽  
Cell Responses

Elicitation of lung tissue-resident memory CD8 T cells (TRMs) is a goal of T-cell based vaccines against respiratory viral pathogens such as influenza A virus (IAV). Chemokine receptor 2 (CCR2)-dependent monocyte trafficking plays an essential role in the establishment of CD8 TRMs in lungs of IAV-infected mice. Here, we used a combination adjuvant-based subunit vaccine strategy that evokes multifaceted (TC1/TC17/TH1/TH17) IAV nucleoprotein-specific lung TRMs, to determine whether CCR2 and monocyte infiltration are essential for vaccine-induced TRM development and protective immunity to IAV in lungs. Following intranasal vaccination, neutrophils, monocytes, conventional dendrtitic cells (DCs) and monocyte-derived DCs internalized and processed vaccine antigen in lungs. We also found that Basic Leucine Zipper ATF-Like Transcription Factor 3 (BATF-3)-dependent DCs were essential for eliciting T cell responses, but CCR2 deficiency enhanced the differentiation of CD127HI/KLRG-1LO, OX40+veCD62L+ve and mucosally imprinted CD69+veCD103+ve effector and memory CD8 T cells in lungs and airways of vaccinated mice. Mechanistically, increased development of lung TRMs, induced by CCR2 deficiency was linked to dampened expression of T-bet, but not altered TCF-1 levels or T cell receptor signaling in CD8 T cells. T1/T17 functional programming, parenchymal localization of CD8/CD4 effector and memory T cells, recall T cell responses and protective immunity to a lethal IAV infection were unaffected in CCR2-deficient mice. Taken together, we identified a negative regulatory role for CCR2 and monocyte trafficking in mucosal imprinting and differentiation of vaccine-induced TRMs. Mechanistic insights from this study may aid the development of T-cell-based vaccines against respiratory viral pathogens including IAV and SARS-CoV-2.

scholarly journals Ex vivo detection of SARS-CoV-2-specific CD8+ T cells: rapid induction, prolonged contraction, and formation of functional memory

2020 ◽  
Author(s):  
Isabel Schulien ◽  
Janine Kemming ◽  
Valerie Oberhardt ◽  
Katharina Wild ◽  
Lea M. Seidel ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Ex Vivo ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Memory Cd8 T Cells ◽  
Cell Responses ◽  
Rapid Induction ◽  
Specific Memory

AbstractCD8+ T cells are critical for the elimination and long-lasting protection of many viral infections, but their role in the current SARS-CoV-2 pandemic is unclear. Emerging data indicates that SARS-CoV-2-specific CD8+ T cells are detectable in the majority of individuals recovering from SARS-CoV-2 infection. However, optimal virus-specific epitopes, the role of pre-existing heterologous immunity as well as their kinetics and differentiation program during disease control have not been defined in detail. Here, we show that both pre-existing and newly induced SARS-CoV-2-specific CD8+ T-cell responses are potentially important determinants of immune protection in mild SARS-CoV-2 infection. In particular, our results can be summarized as follows: First, immunodominant SARS-CoV-2-specific CD8+ T-cell epitopes are targeted in the majority of individuals with convalescent SARS-CoV-2 infection. Second, MHC class I tetramer analyses revealed the emergence of phenotypically diverse and functionally competent pre-existing and newly induced SARS-CoV-2-specific memory CD8+ T cells that showed similar characteristics compared to influenza-specific CD8+ T cells. Third, SARS-CoV-2-specific CD8+ T-cell responses are more robustly detectable than antibodies against the SARS-CoV-2-spike protein. This was confirmed in a longitudinal analysis of acute-resolving infection that demonstrated rapid induction of the SARS-CoV-2-specific CD8+ T cells within a week followed by a prolonged contraction phase that outlasted the waning humoral immune response indicating that CD8+ T-cell responses might serve as a more precise correlate of antiviral immunity than antibody measurements after convalescence. Collectively, these data provide new insights into the fine specificity, heterogeneity, and dynamics of SARS-CoV-2-specific memory CD8+ T cells, potentially informing the rational development of a protective vaccine against SARS-CoV-2.

Leukemia-Associated Antigen Specific T-Cell Responses Following Combined PR1 and WT1 Peptide Vaccination in Patients with Myeloid Malignancies.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 287-287 ◽  
Author(s):  
Katayoun Rezvani ◽  
Agnes S.M. Yong ◽  
Stephan Mielke ◽  
Bipin N. Savani ◽  
Laura Musse ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
T Cell Response ◽  
Post Vaccination ◽  
Myeloid Malignancies ◽  
Cell Responses ◽  
Ifn Γ

Abstract The graft-versus-leukemia (GVL) effect following allogeneic stem cell transplantation (SCT) is evidence that T lymphocytes can eradicate leukemia. The successful identification of a range of leukemia-associated antigens such as proteinase 3 (PR3) and Wilms tumour-1 (WT1) has stimulated efforts to induce leukemia-specific T-cell responses to these antigens using peptide vaccines. Here we describe the safety and immunogenicity of a combined vaccine of two leukemia-associated antigenic peptides, PR1 and WT1. Eight HLA-A*0201 positive patients with myeloid malignancies (2 myelodysplasia, 5 acute myeloid leukemia and 1 chronic myeloid leukemia) received one subcutaneous dose each of PR1 and WT1 vaccines in Montanide adjuvant, with granulocyte-macrophage colony-stimulating factor (GM-CSF). All patients completed 4 weeks follow-up to monitor toxicity and immunological responses. Toxicity was limited to grade 1–2. All remain alive at a median of 252 days (range 105–523). We analyzed the immunological response to vaccination using PR1/HLA-A*0201 and WT1/HLA-A*0201 tetrameric complexes and flow cytometry for intracellular interferon-gamma (IFN-γ) in samples obtained pre- and weekly post-vaccination. A significant CD8+ T-cell response to the vaccine was defined as the emergence of PR1 or WT1-specific CD8+ T-cells when the pre-study analysis was negative or a twofold increase in frequencies when responses were present pre-vaccination. Following vaccination, a significant CD8+ T-cell response to PR1 was seen in 7/8 patients (median 0.34%, range 0.04–0.48%), to WT1 in 5/8 patients (median 0.29%, range 0–0.42%) and to one or both antigens in 8/8 patients. Vaccine-induced CD8+ T-cells were seen as early as 1 week post-vaccination, produced IFN-γ and were preferentially expanded in the effector compartment (CD45RO+/-CD27−). Post-vaccination, there was a strong correlation between the emergence of PR1 or WT1+CD8+ T-cells and a reduction in WT1 mRNA expression, a marker of minimal residual disease, suggesting a vaccine-driven anti-leukemia effect. Loss of response was associated with reappearance of WT1 transcripts (P<0.01). Two patients with detectable CD8+ T-cell responses to PR1 who failed to have a reduction in MRD relapsed 3–6 months following completion of vaccination. This is the first demonstration that a combined PR1 and WT1 vaccine is immunogenic. Based on these results we have initiated a phase 2 study of repeated vaccination with PR1 and WT1 peptides in patients with myeloid malignancies.

scholarly journals Role of Tumor Necrosis Factor Receptors in Regulating CD8 T-Cell Responses during Acute Lymphocytic Choriomeningitis Virus Infection

2005 ◽  
Vol 79 (1) ◽  
pp. 202-213 ◽  
Author(s):  
M. Suresh ◽  
Anju Singh ◽  
Christopher Fischer
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Tumor Necrosis ◽  
Cd8 T Cell ◽  
T Cell Response ◽  
Memory Cd8 T Cells ◽  
Cell Responses ◽  
Necrosis Factor

ABSTRACT The role of tumor necrosis factor (TNF) in regulating various phases of the antiviral T-cell response is incompletely understood. Additionally, despite strong evidence ascribing a role for TNF in protecting against T-cell-dependent autoimmunity, the underlying mechanisms are still obscure. To address these issues, we have investigated the role of tumor necrosis factor receptors (TNFRs) I (p55R) and II (p75R) in regulating CD8 T-cell responses to lymphocytic choriomeningitis virus (LCMV) with wild-type, p55R-deficient (p55−/−), p75R-deficient (p75−/−), and p55R- and p75R-deficient (DKO) mice. Loss of p55R increased the number of memory CD8 T cells to only one of the two immunodominant epitopes, and p75R deficiency had a minimal impact on the T-cell response to LCMV. Strikingly, deficiency of both p55R and p75R had a more dramatic effect on the LCMV-specific CD8 T-cell response; in the DKO mice, as a sequel to enhanced expansion and a reduction in contraction of CD8 T cells, there was a substantial increase in the number of memory CD8 T cells (specific to the two immunodominant epitopes). While the majority of LCMV-specific memory CD8 T cells in wild-type mice were CD62Lhi CCR7hi (central memory), a major proportion of memory CD8 T cells in DKO mice were CD62Llo CCR7hi. TNFR deficiency did not affect the proliferative renewal of memory CD8 T cells. Taken together, these data suggested that TNFRs p55R and p75R have overlapping roles in downregulating CD8 T-cell responses and establishment of immune homeostasis during an acute viral infection.

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