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On the Role of CD8⁺ T Cells in Determining Recovery Time from Influenza Virus Infection.

ABSTRACT: Myriad experiments have identified an important role for CD8⁺ T cell response mechanisms in determining recovery from influenza A virus infection. Animal models of influenza infection further implicate multiple elements of the immune response in defining the dynamical characteristics of viral infection. To date, influenza virus models, while capturing particular aspects of the natural infection history, have been unable to reproduce the full gamut of observed viral kinetic behavior in a single coherent framework. Here, we introduce a mathematical model of influenza viral dynamics incorporating innate, humoral, and cellular immune components and explore its properties with a particular emphasis on the role of cellular immunity. Calibrated against a range of murine data, our model is capable of recapitulating observed viral kinetics from a multitude of experiments. Importantly, the model predicts a robust exponential relationship between the level of effector CD8⁺ T cells and recovery time, whereby recovery time rapidly decreases to a fixed minimum recovery time with an increasing level of effector CD8⁺ T cells. We find support for this relationship in recent clinical data from influenza A (H7N9) hospitalized patients. The exponential relationship implies that people with a lower level of naive CD8⁺ T cells may receive significantly more benefit from induction of additional effector CD8⁺ T cells arising from immunological memory, itself established through either previous viral infection or T cell-based vaccines.

SUBMITTER: Cao P

PROVIDER: S-EPMC5167728 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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On the Role of CD8<sup>+</sup> T Cells in Determining Recovery Time from Influenza Virus Infection.

Cao Pengxing P Wang Zhongfang Z Yan Ada W C AW McVernon Jodie J Xu Jianqing J Heffernan Jane M JM Kedzierska Katherine K McCaw James M JM

Frontiers in immunology 20161220

Myriad experiments have identified an important role for CD8<sup>+</sup> T cell response mechanisms in determining recovery from influenza A virus infection. Animal models of influenza infection further implicate multiple elements of the immune response in defining the dynamical characteristics of viral infection. To date, influenza virus models, while capturing particular aspects of the natural infection history, have been unable to reproduce the full gamut of observed viral kinetic behavior in ...[more]

PMID: 28066421

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Project description:CD8+ T cells recognizing antigenic peptides derived from conserved internal viral proteins confer broad protection against distinct influenza viruses. As memory CD8+ T cells change throughout the human lifetime and across tissue compartments, we investigated how T cell receptor (TCR) composition and diversity relate to memory CD8+ T cells across anatomical sites and immunological phases of human life. We used ex vivo peptide-HLA tetramer magnetic enrichment, single-cell multiplex RT-PCR for both the TCR-alpha (TCRα) and TCR-beta (TCRβ) chains, and new TCRdist and grouping of lymphocyte interactions by paratope hotspots (GLIPH) algorithms to compare TCRs directed against the most prominent human influenza epitope, HLA-A*02:01-M158-66 (A2+M158). We dissected memory TCR repertoires directed toward A2+M158 CD8+ T cells within human tissues and compared them to human peripheral blood of young and elderly adults. Furthermore, we compared these memory CD8+ T cell repertoires to A2+M158 CD8+ TCRs during acute influenza disease in patients hospitalized with avian A/H7N9 virus. Our study provides the first ex vivo comparative analysis of paired antigen-specific TCR-α/β clonotypes across different tissues and peripheral blood across different age groups. We show that human A2+M158 CD8+ T cells can be readily detected in human lungs, spleens, and lymph nodes, and that tissue A2+M158 TCRαβ repertoires reflect A2+M158 TCRαβ clonotypes derived from peripheral blood in healthy adults and influenza-infected patients. A2+M158 TCRαβ repertoires displayed distinct features only in elderly adults, with large private TCRαβ clonotypes replacing the prominent and public TRBV19/TRAV27 TCRs. Our study provides novel findings on influenza-specific TCRαβ repertoires within human tissues, raises the question of how we can prevent the loss of optimal TCRαβ signatures with aging, and provides important insights into the rational design of T cell-mediated vaccines and immunotherapies.

Dataset Information

On the Role of CD8⁺ T Cells in Determining Recovery Time from Influenza Virus Infection.

Publications

On the Role of CD8<sup>+</sup> T Cells in Determining Recovery Time from Influenza Virus Infection.

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Dataset Information

On the Role of CD8+ T Cells in Determining Recovery Time from Influenza Virus Infection.

Publications

On the Role of CD8<sup>+</sup> T Cells in Determining Recovery Time from Influenza Virus Infection.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

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On the Role of CD8⁺ T Cells in Determining Recovery Time from Influenza Virus Infection.