scholarly journals Memory CD4+ T-cell–mediated protection depends on secondary effectors that are distinct from and superior to primary effectors

2012 ◽  
Vol 109 (38) ◽  
pp. E2551-E2560 ◽  
Author(s):  
Tara M. Strutt ◽  
K. Kai McKinstry ◽  
Yi Kuang ◽  
Linda M. Bradley ◽  
Susan L. Swain
Keyword(s):  
T Cell ◽  
Influenza A Virus ◽  
Influenza A ◽  
Expression Patterns ◽  
Memory Cell ◽  
Specific Expression ◽  
Follicular Helper ◽  
Organ Specific ◽  
Follicular Helper T Cell ◽  
And Migration

Whether differences between naive cell-derived primary (1°) and memory cell-derived secondary (2°) CD4+ T-cell effectors contribute to protective recall responses is unclear. Here, we compare these effectors directly after influenza A virus infection. Both develop with similar kinetics, but 2° effectors accumulate in greater number in the infected lung and are the critical component of memory CD4+ T-cell–mediated protection against influenza A virus, independent of earlier-acting memory-cell helper functions. Phenotypic, functional, and transcriptome analyses indicate that 2° effectors share organ-specific expression patterns with 1° effectors but are more multifunctional, with more multicytokine (IFN-γ+/IL-2+/TNF+)-producing cells and contain follicular helper T-cell populations not only in the spleen and draining lymph nodes but also in the lung. In addition, they express more CD127 and NKG2A but less ICOS and Lag-3 than 1° effectors and express higher levels of several genes associated with survival and migration. Targeting two differentially expressed molecules, NKG2A and Lag-3, reveals differential regulation of 1° and 2° effector functions during pathogen challenge.

scholarly journals Tbx21 and Foxp3 Are Epigenetically Stabilized in T-Bet+ Tregs That Transiently Accumulate in Influenza A Virus-Infected Lungs

2021 ◽  
Vol 22 (14) ◽  
pp. 7522
Author(s):  
Yassin Elfaki ◽  
Juhao Yang ◽  
Julia Boehme ◽  
Kristin Schultz ◽  
Dunja Bruder ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Influenza A Virus ◽  
Influenza A ◽  
T Cell Subsets ◽  
T Helper 1 ◽  
T Box ◽  
Cell Responses ◽  
Accumulation Kinetics ◽  
Kinetics Of

During influenza A virus (IAV) infections, CD4+ T cell responses within infected lungs mainly involve T helper 1 (Th1) and regulatory T cells (Tregs). Th1-mediated responses favor the co-expression of T-box transcription factor 21 (T-bet) in Foxp3+ Tregs, enabling the efficient Treg control of Th1 responses in infected tissues. So far, the exact accumulation kinetics of T cell subsets in the lungs and lung-draining lymph nodes (dLN) of IAV-infected mice is incompletely understood, and the epigenetic signature of Tregs accumulating in infected lungs has not been investigated. Here, we report that the total T cell and the two-step Treg accumulation in IAV-infected lungs is transient, whereas the change in the ratio of CD4+ to CD8+ T cells is more durable. Within lungs, the frequency of Tregs co-expressing T-bet is steadily, yet transiently, increasing with a peak at Day 7 post-infection. Interestingly, T-bet+ Tregs accumulating in IAV-infected lungs displayed a strongly demethylated Tbx21 locus, similarly as in T-bet+ conventional T cells, and a fully demethylated Treg-specific demethylated region (TSDR) within the Foxp3 locus. In summary, our data suggest that T-bet+ but not T-bet− Tregs are epigenetically stabilized during IAV-induced infection in the lung.

scholarly journals Follicular Helper T Cell Differentiation Requires Continuous Antigen Presentation that Is Independent of Unique B Cell Signaling

Immunity ◽  
2010 ◽  
Vol 33 (2) ◽  
pp. 241-253 ◽  
Author(s):  
Elissa K. Deenick ◽  
Anna Chan ◽  
Cindy S. Ma ◽  
Dominique Gatto ◽  
Pamela L. Schwartzberg ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
T Cell ◽  
Cell Signaling ◽  
B Cell ◽  
Antigen Presentation ◽  
T Cell Differentiation ◽  
Helper T Cell ◽  
B Cell Signaling ◽  
Follicular Helper ◽  
Follicular Helper T Cell

Influenza type A virus M protein expression on infected cells is responsible for cross-reactive recognition by cytotoxic thymus-derived lymphocytes

1980 ◽  
Vol 29 (2) ◽  
pp. 719-723 ◽  
Author(s):  
C S Reiss ◽  
J L Schulman
Keyword(s):  
T Cell ◽  
Influenza A Virus ◽  
Influenza A ◽  
Rabbit Antiserum ◽  
Type A ◽  
M Protein ◽  
Cytotoxic T Cell ◽  
Influenza A Viruses ◽  
Infected Cells ◽  
Cytotoxic T Cell Responses

M protein of influenza A virus was detected with rabbit antiserum by both indirect immunofluorescence and by antibody plus complement-mediated cytolysis on the cell surfaces of both productively and nonproductively infected cells. In contrast, antiserum to nucleoprotein failed to react with unfixed infected cells, but did bind to fixed infected cells, especially in the perinuclear area. Incorporation of antiserum to M protein in a T-cell-mediated cytotoxicity assay produced almost complete abrogation of lysis of H-2-compatible cells infected with an influenza A virus of a subtype which differed from that used to elicit the cytotoxic T cells. However, the antibody did not significantly block 51Cr release from cells infected with the homotypic type A influenza virus. These observations are in accord with the hypothesis that the cross-reactive cytotoxic T-cell responses seen with cells infected by heterotypic influenza A viruses are due to recognition of a common M protein.

scholarly journals Why Are CD8 T Cell Epitopes of Human Influenza A Virus Conserved?

2018 ◽  
Author(s):  
Zheng-Rong Tiger Li ◽  
Veronika I. Zarnitsyna ◽  
Anice C. Lowen ◽  
Daniel Weissman ◽  
Katia Koelle ◽  
...  
Keyword(s):  
T Cell ◽  
Influenza A Virus ◽  
Influenza A ◽  
Cd8 T Cell ◽  
Influenza Vaccines ◽  
T Cell Epitopes ◽  
Word Count ◽  
Mhc I ◽  
Escape Variant ◽  
Replicative Fitness

AbstractThe high-degree conservation of CD8 T cell epitopes of influenza A virus (IAV) may allow T cell-inducing vaccines effective across different strains and subtypes. This conservation is not fully explained by functional constraint, since additional mutation(s) can compensate the replicative fitness loss of IAV escape-variant. Here, we propose three additional mechanisms that contribute to the conservation of CD8 T cell epitopes of IAV. First, influenza-specific CD8 T cells may protect predominantly against severe pathology rather than infection and may only have a modest effect on transmission. Second, polymorphism of human MHC-I gene restricts the advantage of an escape-variant to only a small fraction of human population, who carry the relevant MHC-I alleles. Finally, infection with CD8 T cell-escapevariants may result in compensatory increase in the responses to other epitopes of IAV. A combination of population genetics and epidemiological models is used to examine how the interplay between these mechanisms affects the rate of invasion of IAV escape-variants. We conclude that the invasion of an escape-variant will be very slow with a timescale of decades or longer, even if the escape-variant does not have a replicative fitness loss. Our results suggest T cell-inducing vaccines may not engender the rapid evolution of IAV and serve as a foundation for future modeling works on the long-term effectiveness and impacts of T cell-inducing influenza vaccines. (Word count: 221)ImportanceUniversal influenza vaccines against the conserved epitopes of influenza A virus have been proposed to minimize the burden of seasonal outbreaks and prepare for the pandemics. However, it is not clear to which extent the T cell-inducing vaccines will select for viruses that escape the T cell responses. Our mathematical models suggest how the nature of CD8 T cell protection contributes to the conservation of the CD8 T cell epitopes of influenza A virus. Also, it points out the essential biological parameters and questions that need addressing by future experimental works. (Word count: 91)

scholarly journals CD4+T Cells: Differentiation and Functions

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Rishi Vishal Luckheeram ◽  
Rui Zhou ◽  
Asha Devi Verma ◽  
Bing Xia
Keyword(s):  
T Cells ◽  
Transcription Factors ◽  
T Cell ◽  
Cytokine Signaling ◽  
T Helper ◽  
T Helper 1 ◽  
T Helper 17 ◽  
Differentiated Cells ◽  
Follicular Helper ◽  
Follicular Helper T Cell

CD4+T cells are crucial in achieving a regulated effective immune response to pathogens. Naive CD4+T cells are activated after interaction with antigen-MHC complex and differentiate into specific subtypes depending mainly on the cytokine milieu of the microenvironment. Besides the classical T-helper 1 and T-helper 2, other subsets have been identified, including T-helper 17, regulatory T cell, follicular helper T cell, and T-helper 9, each with a characteristic cytokine profile. For a particular phenotype to be differentiated, a set of cytokine signaling pathways coupled with activation of lineage-specific transcription factors and epigenetic modifications at appropriate genes are required. The effector functions of these cells are mediated by the cytokines secreted by the differentiated cells. This paper will focus on the cytokine-signaling and the network of transcription factors responsible for the differentiation of naive CD4+T cells.

SATB1 Expression Governs Follicular Helper T-cell-Triggered Tertiary Lymphoid Structure Assembly

2021 ◽  
Author(s):  
Ricardo A. Chaurio ◽  
Carmen M. Anadon ◽  
Tara L. Costich ◽  
Kyle K. Payne ◽  
Subir Biswas ◽  
...  
Keyword(s):  
T Cell ◽  
Helper T Cell ◽  
Follicular Helper ◽  
Follicular Helper T Cell ◽  
Satb1 Expression ◽  
Structure Assembly
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