scholarly journals Low dose mRNA-1273 COVID-19 vaccine generates durable T cell memory and antibodies enhanced by pre-existing crossreactive T cell memory

2021 ◽  
Author(s):  
Jose Mateus ◽  
Jennifer M Dan ◽  
Zeli Zhang ◽  
Carolyn Rydyznski Moderbacher ◽  
Marshall Lammers ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Low Dose ◽  
Age Groups ◽  
Cd8 T Cell ◽  
Antibody Responses ◽  
Cd4 T Cell ◽  
T Cell Memory ◽  
Cell Memory

Understanding human immune responses to SARS-CoV-2 RNA vaccines is of interest for a panoply of reasons. Here we examined vaccine-specific CD4+ T cell, CD8+ T cell, binding antibody, and neutralizing antibody responses to the 25 ug Moderna mRNA-1273 vaccine over 7 months post-immunization, including multiple age groups, with a particular interest in assessing whether pre-existing crossreactive T cell memory impacts vaccine-generated immunity. Low dose (25 ug) mRNA-1273 elicited durable Spike binding antibodies comparable to that of convalescent COVID-19 cases. Vaccine-generated Spike memory CD4+ T cells 6 months post-boost were comparable in quantity and quality to COVID-19 cases, including the presence of TFH cells and IFNg-expressing cells. Spike CD8+ T cells were generated in 88% of subjects, with equivalent percentages of CD8+ T cell memory responders at 6 months post-boost compared to COVID-19 cases. Lastly, subjects with pre-existing crossreactive CD4+ T cell memory had increased CD4+ T cell and antibody responses to the vaccine, demonstrating a biological relevance of SARS-CoV-2 crossreactive CD4+ T cells.

scholarly journals CD4 + T‐cell memory: generation and multi‐faceted roles for CD4 + T cells in protective immunity to influenza

2006 ◽  
Vol 211 (1) ◽  
pp. 8-22 ◽  
Author(s):  
Susan L. Swain ◽  
Javed N. Agrewala ◽  
Deborah M. Brown ◽  
Dawn M. Jelley‐Gibbs ◽  
Susanne Golech ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Protective Immunity ◽  
Cd4 T Cell ◽  
T Cell Memory ◽  
Cell Memory

scholarly journals OX40 Ligation of CD4+T Cells Enhances Virus-Specific CD8+T Cell Memory Responses Independently of IL-2 and CD4+T Regulatory Cell Inhibition

2006 ◽  
Vol 176 (4) ◽  
pp. 2486-2495 ◽  
Author(s):  
Qigui Yu ◽  
Feng Yun Yue ◽  
Xiao X. Gu ◽  
Herbert Schwartz ◽  
Colin M. Kovacs ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Cd8 T Cell ◽  
T Cell Memory ◽  
T Regulatory Cell ◽  
Cell Memory ◽  
Regulatory Cell ◽  
Cd8 T Cell Memory ◽  
Cell Inhibition

Primary immune responses to human CMV: a critical role for IFN-γ–producing CD4+ T cells in protection against CMV disease

Blood ◽  
2003 ◽  
Vol 101 (7) ◽  
pp. 2686-2692 ◽  
Author(s):  
Laila E. Gamadia ◽  
Ester B. M. Remmerswaal ◽  
Jan F. Weel ◽  
Frederieke Bemelman ◽  
René A. W. van Lier ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Response ◽  
Cd4 T Cells ◽  
Critical Role ◽  
Cd8 T Cell ◽  
T Cell Response ◽  
Antibody Responses ◽  
Cd4 T Cell ◽  
Effector Memory

The correlates of protective immunity to disease-inducing viruses in humans remain to be elucidated. We determined the kinetics and characteristics of cytomegalovirus (CMV)–specific CD4+ and CD8+ T cells in the course of primary CMV infection in asymptomatic and symptomatic recipients of renal transplants. Specific CD8+ cytotoxic T lymphocyte (CTL) and antibody responses developed regardless of clinical signs. CD45RA−CD27+CCR7− CTLs, although classified as immature effector cells in HIV infection, were the predominant CD8 effector population in the acute phase of protective immune reactions to CMV and were functionally competent. Whereas in asymptomatic individuals the CMV-specific CD4+ T-cell response preceded CMV-specific CD8+T-cell responses, in symptomatic individuals the CMV-specific effector-memory CD4+ T-cell response was delayed and only detectable after antiviral therapy. The appearance of disease symptoms in these patients suggests that functional CD8+ T-cell and antibody responses are insufficient to control viral replication and that formation of effector-memory CD4+ T cells is necessary for recovery of infection.

scholarly journals Mini-review CD4 T cells are required for CD8 T cell memory generation

2003 ◽  
Vol 33 (12) ◽  
pp. 3225-3231 ◽  
Author(s):  
Christine Bourgeois ◽  
Corinne Tanchot
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Cd8 T Cell ◽  
T Cell Memory ◽  
Cell Memory ◽  
Cd8 T Cell Memory

scholarly journals Anti-apoptotic clone 11 derived peptides induce in vitro death of CD4+ T cells susceptible to HIV-1 infection

2020 ◽  
Author(s):  
Anastassia Mikhailova ◽  
José Carlos Valle-Casuso ◽  
Annie David ◽  
Valérie Monceaux ◽  
Stevenn Volant ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
T Cell Subsets ◽  
Cd4 T Cell ◽  
T Cell Memory ◽  
Target Cells ◽  
Cell Memory ◽  
Infected Cells ◽  
Hiv 1

ABSTRACTHIV-1 successfully establishes long-term infection in its target cells despite viral cytotoxic effects. We have recently shown that cell metabolism is an important factor driving CD4+ T-cell susceptibility to HIV-1 and the survival of infected cells. We show here that expression of anti-apoptotic clone 11 (AAC-11), an anti-apoptotic factor upregulated in many cancers, increased with progressive CD4+ T cell memory differentiation in association with the expression of cell cycle, activation and metabolism genes and correlated with susceptibility to HIV-1 infection. Synthetic peptides based on the LZ domain sequence of AAC-11, responsible for its interaction with molecular partners, were previously shown to be cytotoxic to cancer cells. Here we observed that these peptides also blocked HIV-1 infection by inducing cell death of HIV-1 susceptible primary CD4+ T-cells across all T-cell subsets. The peptides targeted metabolically active cells and had the greatest effect on effector and transitional CD4+ T cell memory subsets. Our results suggest that AAC-11 survival pathway is potentially involved in the survival of HIV-1 infectable cells and provide a proof of principle that some cellular characteristics can be targeted to eliminate the cells offering the best conditions to sustain HIV-1 replication.IMPORTANCEAlthough antiretroviral treatment efficiently blocks HIV multiplication, it cannot eliminate the cells already carrying integrated proviruses. In the search for a HIV cure the identification of new potential targets to selectively eliminate infected cells is of the outmost importance. We show here that peptides derived from the anti-apoptotic clone 11 (AAC-11), which expression levels correlated with susceptibility to HIV-1 infection of CD4+ T-cells, induced cytotoxicity in CD4+ T-cells showing the highest levels of activation and metabolic activity, conditions known to favor HIV-1 infection. Accordingly, CD4+ T-cells that survived the cytotoxic action of the AAC-11 peptides were resistant to HIV-1 replication. Our results identify a new potential molecular pathway to target HIV-1 infection.

scholarly journals CD8 T Cell Memory Recall Is Enhanced by Novel Direct Interactions with CD4 T Cells Enabled by MHC Class II Transferred from APCs

PLoS ONE ◽  
2013 ◽  
Vol 8 (2) ◽  
pp. e56999 ◽  
Author(s):  
Pablo A. Romagnoli ◽  
Mary F. Premenko-Lanier ◽  
Gilbert D. Loria ◽  
John D. Altman
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mhc Class Ii ◽  
Cd4 T Cells ◽  
Cd8 T Cell ◽  
Class Ii ◽  
T Cell Memory ◽  
Memory Recall ◽  
Cell Memory ◽  
Cd8 T Cell Memory

scholarly journals The multifaceted role of CD4+ T cells in CD8+ T cell memory

2016 ◽  
Vol 16 (2) ◽  
pp. 102-111 ◽  
Author(s):  
Brian J. Laidlaw ◽  
Joseph E. Craft ◽  
Susan M. Kaech
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Cd8 T Cell ◽  
T Cell Memory ◽  
Cell Memory ◽  
Cd8 T Cell Memory

scholarly journals Multiple developmental pathways lead to the generation of CD4 T-cell memory

2020 ◽  
Vol 32 (9) ◽  
pp. 589-595 ◽  
Author(s):  
Shintaro Hojyo ◽  
Damon Tumes ◽  
Akihiko Murata ◽  
Koji Tokoyoda
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Memory Cell ◽  
Cd4 T Cell ◽  
Developmental Pathways ◽  
T Cell Memory ◽  
Cell Memory ◽  
Memory Cd4 T Cells

Abstract Long-term immunological memory mediated by CD4 T cells provides a rapid protection against previously encountered pathogens or antigens. However, it is still controversial how memory CD4 T cells are generated and maintained. Unclear definitions of T-cell memory may be partially responsible for this controversy. It is becoming clear that diverse pathways are responsible for the differentiation and long-term persistence of memory T cells. We herein discuss the diversity of memory cell generation, describing a novel population of resting memory CD4 T cells and their precursors.

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