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 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 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 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 The Role of CD4 T Cell Memory in Generating Protective Immunity to Novel and Potentially Pandemic Strains of Influenza

2016 ◽  
Vol 7 ◽  
Author(s):  
Anthony DiPiazza ◽  
Katherine A. Richards ◽  
Zackery A. G. Knowlden ◽  
Jennifer L. Nayak ◽  
Andrea J. Sant
Keyword(s):  
T Cell ◽  
Protective Immunity ◽  
Cd4 T Cell ◽  
T Cell Memory ◽  
Cell Memory ◽  
Pandemic Strains

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

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 CD4 T Cell Responses in Lung Tissue and Their Role in Th2 Protective Immunity

2021 ◽  
Author(s):  
◽  
Marina Catherine Goudie Harvie
Keyword(s):  
T Cells ◽  
Lymph Node ◽  
T Cell ◽  
Lung Tissue ◽  
Cd4 T Cells ◽  
Lymphoid Tissue ◽  
Protective Immunity ◽  
Cd4 T Cell ◽  
Cell Responses ◽  
Memory Cd4 T Cells

<p>The acquisition of protective immunity is a critical feature of the immune system. It is the unique ability of the adaptive immune response to generate and maintain long-lived antigen specific memory cells, which is the key to preventing reinfection and achieving the goal of protective immunity. The importance of secondary lymphoid tissue (such as lymph nodes) as a site of effector CD4 T cell responses and the generation, dissemination and maintenance of memory CD4 T cells is well accepted. However, a key research area needing investigation is the basic biology of the CD4 T cell, particularly the recirculation, distribution and maintenance of CD4 T cells at sites throughout the body. To address these issues we used Nippostrongylus brasiliensis as a model of CD4 mediated protective immunity, combined with G4/IL-4 reporter mice. We show that the lung environment is critical for the priming of CD4 T cells and conferring protective immunity. In contrast to others we find no protective role for the CD4 T cell population of the skin and only a minor role for the population within the gut. In a separate study we used the drug fingolimod (FTY720) to block the cellular trafficking between lymph node and lung tissue during immune responses. Interestingly, our findings show that protection against N. brasiliensis infection is maintained when CD4 T cell recirculation between the lung and lymph node is blocked. Furthermore, we reveal that peripheral lung residing CD4 T cells are sufficient for conferring protective immunity in the N. brasiliensis model, generating support for the model of effector lymphoid tissue. When N. brasiliensis experienced CD4 T cells were localised to the lung by intranasal adoptive transfer they were able to confer protection against infection in otherwise naive animals, as early as 48 hours post infection. The most striking finding of this work is the discovery that memory CD4 T cells residing in the lung that are sufficient to confer protection against reinfection. Identifying the factors in the lung and lymph node that induce and support this CD4 T cell subset will be an important area of future research given its high relevance to the design of vaccines against parasite infections.</p>

scholarly journals In vivo antigen expression regulates CD4 T cell differentiation and vaccine efficacy against Mycobacterium tuberculosis infection

2021 ◽  
Author(s):  
Helena Strand Clemmensen ◽  
Jean-Yves Dube ◽  
Fiona McIntosh ◽  
Ida Rosenkrands ◽  
Gregers Jungersen ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Differentiation ◽  
T Cell ◽  
Cd4 T Cells ◽  
Protective Immunity ◽  
Antigen Expression ◽  
T Cell Differentiation ◽  
Cd4 T Cell ◽  
Protective Capacity

AbstractNew vaccines are urgently needed against Mycobacterium tuberculosis (Mtb), which kills more than 1.4 million people each year. CD4 T cell differentiation is a key determinant of protective immunity against Mtb, but it is not fully understood how host-pathogen interactions shape individual antigen-specific T cell populations and their protective capacity. Here, we investigated the immunodominant Mtb antigen, MPT70, which is upregulated in response to IFN-γ or nutrient/oxygen deprivation of in vitro infected macrophages. Using a murine aerosol infection model, we compared the in vivo expression kinetics of MPT70 to a constitutively expressed antigen, ESAT-6, and analysed their corresponding CD4 T cell phenotype and vaccine-protection. For wild-type Mtb, we found that in vivo expression of MPT70 was delayed compared to ESAT-6. This delayed expression was associated with induction of less differentiated MPT70-specific CD4 T cells but, compared to ESAT-6, also reduced protection after vaccination. In contrast, infection with an MPT70-overexpressing Mtb strain promoted highly differentiated KLRG1+CX3CR1+ CD4 T cells with limited lung-homing capacity. Importantly, this differentiated phenotype could be prevented by vaccination and, against the overexpressing strain, vaccination with MPT70 conferred similar protection as ESAT-6. Together our data indicate that high in vivo antigen expression drives T cells towards terminal differentiation and that targeted vaccination with adjuvanted protein can counteract this phenomenon by maintaining T cells in a protective less-differentiated state. These observations shed new light on host-pathogen interactions and provide guidance on how future Mtb vaccines can be designed to tip the immune-balance in favor of the host.ImportanceTuberculosis, caused by Mtb, constitutes a global health crisis of massive proportions and the impact of the current COVID-19 pandemic is expected to cause a rise in tuberculosis-related deaths. Improved vaccines are therefore needed more than ever, but a lack of knowledge on protective immunity hampers their development. The present study shows that constitutively expressed antigens with high availability drive highly differentiated CD4 T cells with diminished protective capacity, which could be a survival strategy by Mtb to evade T cell immunity against key antigens. We demonstrate that immunisation with such antigens can counteract this phenomenon by maintaining antigen-specific T cells in a state of low differentiation. Future vaccine strategies should therefore explore combinations of multiple highly expressed antigens and we suggest that T cell differentiation could be used as a readily measurable parameter to identify these in both preclinical and clinical studies.

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