scholarly journals Memory CD4 T cell subsets are kinetically heterogeneous and replenished from naive T cells at high levels

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Graeme Gossel ◽  
Thea Hogan ◽  
Daniel Cownden ◽  
Benedict Seddon ◽  
Andrew J Yates
Keyword(s):  
T Cells ◽  
T Cell ◽  
De Novo ◽  
Memory Cell ◽  
T Cell Subsets ◽  
Cd4 T Cell ◽  
T Cell Memory ◽  
Cell Memory ◽  
Quiescent Cells ◽  
Memory Cd4 T Cells

Characterising the longevity of immunological memory requires establishing the rules underlying the renewal and death of peripheral T cells. However, we lack knowledge of the population structure and how self-renewal and de novo influx contribute to the maintenance of memory compartments. Here, we characterise the kinetics and structure of murine CD4 T cell memory subsets by measuring the rates of influx of new cells and using detailed timecourses of DNA labelling that also distinguish the behaviour of recently divided and quiescent cells. We find that both effector and central memory CD4 T cells comprise subpopulations with highly divergent rates of turnover, and show that inflows of new cells sourced from the naive pool strongly impact estimates of memory cell lifetimes and division rates. We also demonstrate that the maintenance of CD4 T cell memory subsets in healthy mice is unexpectedly and strikingly reliant on this replenishment.

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.

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 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 Limited Model Antigen Expression by Transgenic Fungi Induces Disparate Fates during Differentiation of Adoptively Transferred T Cell Receptor Transgenic CD4+T Cells: Robust Activation and Proliferation with Weak Effector Function during Recall

2011 ◽  
Vol 80 (2) ◽  
pp. 787-797 ◽  
Author(s):  
Marcel Wüthrich ◽  
Karen Ersland ◽  
John C. Pick-Jacobs ◽  
Benjamin H. Gern ◽  
Christopher A. Frye ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Fluorescent Protein ◽  
Antigen Expression ◽  
Cell Receptor ◽  
T Cell Subsets ◽  
T Cell Memory ◽  
Cell Memory

ABSTRACTCD4+T cells are the key players of vaccine resistance to fungi. The generation of effective T cell-based vaccines requires an understanding of how to induce and maintain CD4+T cells and memory. The kinetics of fungal antigen (Ag)-specific CD4+T cell memory development has not been studied due to the lack of any known protective epitopes and clonally restricted T cell subsets with complementary T cell receptors (TCRs). Here, we investigated the expansion and function of CD4+T cell memory after vaccination with transgenic (Tg)Blastomyces dermatitidisyeasts that display a model Ag, Eα-mCherry (Eα-mCh). We report that Tg yeast led to Eα display on Ag-presenting cells and induced robust activation, proliferation, and expansion of adoptively transferred TEa cells in an Ag-specific manner. Despite robust priming by Eα-mCh yeast, antifungal TEa cells recruited and produced cytokines weakly during a recall response to the lung. The addition of exogenous Eα-red fluorescent protein (RFP) to the Eα-mCh yeast boosted the number of cytokine-producing TEa cells that migrated to the lung. Thus, model epitope expression on yeast enables the interrogation of Ag presentation to CD4+T cells and primes Ag-specific T cell activation, proliferation, and expansion. However, the limited availability of model Ag expressed by Tg fungi during T cell priming blunts the downstream generation of effector and memory T cells.

scholarly journals Differential impact of self and environmental antigens on the ontogeny and maintenance of CD4+ T cell memory

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Thea Hogan ◽  
Maria Nowicka ◽  
Daniel Cownden ◽  
Claire F Pearson ◽  
Andrew J Yates ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Subsets ◽  
Cd4 T Cell ◽  
T Cell Memory ◽  
Effector Memory ◽  
Laboratory Mice ◽  
Differential Impact ◽  
Persistent Memory ◽  
Environmental Antigens ◽  
Memory Cd4 T Cells

Laboratory mice develop populations of circulating memory CD4+ T cells in the absence of overt infection. We have previously shown that these populations are replenished from naive precursors at high levels throughout life (Gossel et al., 2017). However, the nature, relative importance and timing of the forces generating these cells remain unclear. Here, we tracked the generation of memory CD4+ T cell subsets in mice housed in facilities differing in their ‘dirtiness’. We found evidence for sequential naive to central memory to effector memory development, and confirmed that both memory subsets are heterogeneous in their rates of turnover. We also inferred that early exposure to self and environmental antigens establishes persistent memory populations at levels determined largely, although not exclusively, by the dirtiness of the environment. After the first few weeks of life, however, these populations are continuously supplemented by new memory cells at rates that are independent of environment.

scholarly journals Antiapoptotic Clone 11-Derived Peptides Induce In Vitro Death of CD4+ T Cells Susceptible to HIV-1 Infection

2020 ◽  
Vol 94 (14) ◽  
Author(s):  
Anastassia Mikhailova ◽  
José Carlos Valle-Casuso ◽  
Annie David ◽  
Valérie Monceaux ◽  
Stevenn Volant ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Subsets ◽  
T Cell Memory ◽  
Target Cells ◽  
Cytotoxic Action ◽  
Cell Memory ◽  
Infected Cells ◽  
Hiv 1

ABSTRACT HIV-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 antiapoptotic clone 11 (AAC-11), an antiapoptotic 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 was 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 the 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 the AAC-11 survival pathway is potentially involved in the survival of HIV-1-infectible cells and provide proof of principle that some cellular characteristics can be targeted to eliminate the cells offering the best conditions to sustain HIV-1 replication. IMPORTANCE Although antiretroviral treatment efficiently blocks HIV multiplication, it cannot eliminate cells already carrying integrated proviruses. In the search for an 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 antiapoptotic clone 11 (AAC-11), whose 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 CD4 T–cell memory can persist in the absence of class II

2000 ◽  
Vol 355 (1395) ◽  
pp. 407-411 ◽  
Author(s):  
Susan L. Swain
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Specific Antigen ◽  
Class Ii ◽  
Cd4 T Cell ◽  
T Cell Memory ◽  
Memory Cells ◽  
Short Period ◽  
Memory Cd4 T Cells

To understand how memory CD4 T cells are generated we have re–examined the requirements for continuing antigen stimulation in the generation and persistence of this population. We find that specific antigen is only required for a short period during the activation of naive CD4 Tcells and is not required for memory generation from activated CD4 T cells or for persistence of resting memory cells generated by transfer of activated CD4 to adoptive hosts. Moreover, transfer of activated CD4 T cells to class–II–deficient hosts, indicates that T cR–class II major histocompatibility interaction is also unnecessary for either the transition from activated CD4 T cell to resting memory cells or for persistence over an eightweek period. Thus the signals regulating generation and maintenance of memory are fundamentally different from those which regulate the expansion of effector CD4 T–cell populations which include antigen itself and the CD4 T–cell autocrine cytokines induced by antigen.

Sign in / Sign up

Export Citation Format

Share Document