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      The impact of aging on CD4 + T cell responses to influenza infection

      review-article
      , ,
      Biogerontology
      Springer Netherlands
      CD4 T cells, Subset differentiation, Influenza, Aging

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          Abstract

          CD4 + T cells are important for generating high quality and robust immune responses to influenza infection. Immunosenescence that occurs with aging, however, compromises the ability of CD4 + T cells to differentiate into functional subsets resulting in a multitude of dysregulated responses namely, delayed viral clearance and prolonged inflammation leading to increased pathology. Current research employing animal models and human subjects has provided new insights into the description and mechanisms of age-related CD4 + T cell changes. In this review, we will discuss the consequences of aging on CD4 + T cell differentiation and function and how this influences the initial CD4 + T cell effector responses to influenza infection. Understanding these age-related alterations will aid in the pharmacological development of therapeutic treatments and improved vaccination strategies for the vulnerable elderly population.

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          Most cited references41

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          Chemokines enhance immunity by guiding naive CD8+ T cells to sites of CD4+ T cell-dendritic cell interaction.

          CD8+ T cells have a crucial role in resistance to pathogens and can kill malignant cells; however, some critical functions of these lymphocytes depend on helper activity provided by a distinct population of CD4+ T cells. Cooperation between these lymphocyte subsets involves recognition of antigens co-presented by the same dendritic cell, but the frequencies of such antigen-bearing cells early in an infection and of the relevant naive T cells are both low. This suggests that an active mechanism facilitates the necessary cell-cell associations. Here we demonstrate that after immunization but before antigen recognition, naive CD8+ T cells in immunogen-draining lymph nodes upregulate the chemokine receptor CCR5, permitting these cells to be attracted to sites of antigen-specific dendritic cell-CD4+ T cell interaction where the cognate chemokines CCL3 and CCL4 (also known as MIP-1alpha and MIP-1beta) are produced. Interference with this actively guided recruitment markedly reduces the ability of CD4+ T cells to promote memory CD8+ T-cell generation, indicating that an orchestrated series of differentiation events drives nonrandom cell-cell interactions within lymph nodes, optimizing CD8+ T-cell immune responses involving the few antigen-specific precursors present in the naive repertoire.
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            Aging of the innate immune system.

            The innate immune system is composed of a network of cells including neutrophils, NK and NKT cells, monocytes/macrophages, and dendritic cells that mediate the earliest interactions with pathogens. Age-associated defects are observed in the activation of all of these cell types, linked to compromised signal transduction pathways including the Toll-like Receptors. However, aging is also characterized by a constitutive pro-inflammatory environment (inflamm-aging) with persistent low-grade innate immune activation that may augment tissue damage caused by infections in elderly individuals. Thus, immunosenescence in the innate immune system appears to reflect dysregulation, rather than exclusively impaired function. Copyright 2010. Published by Elsevier Ltd.
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              Effectors and memories: Bcl-6 and Blimp-1 in T and B lymphocyte differentiation.

              Bcl-6 and Blimp-1 have recently been identified as key transcriptional regulators of effector and memory differentiation in CD4(+) T cells and CD8(+) T cells. Bcl-6 and Blimp-1 were previously known to be critical regulators of effector and memory differentiation of B lymphocytes. The new findings unexpectedly point to the Bcl-6 and Blimp-1 regulatory axis as a ubiquitous mechanism for controlling effector and memory lymphocyte differentiation and function. Bcl-6 and Blimp-1 are antagonistic transcription factors and can function as a self-reinforcing genetic switch for cell-fate decisions. However, their influences in different lymphocytes are complex. Here we review and examine the commonalities and differences in the functions of these transcription factors in CD4(+) follicular helper T(FH) lymphocytes, effector CD8(+) T lymphocytes and B lymphocytes.
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                Author and article information

                Contributors
                860-679-8431 , lhaynes@uchc.edu
                Journal
                Biogerontology
                Biogerontology
                Biogerontology
                Springer Netherlands (Dordrecht )
                1389-5729
                1573-6768
                3 April 2018
                3 April 2018
                2018
                : 19
                : 6
                : 437-446
                Affiliations
                ISNI 0000000419370394, GRID grid.208078.5, UConn Center on Aging and Department of Immunology, , University of Connecticut School of Medicine, ; Farmington, CT 06030 USA
                Author information
                http://orcid.org/0000-0002-5006-3339
                Article
                9754
                10.1007/s10522-018-9754-8
                6170716
                29616390
                6f5f4d6d-10f8-4ca5-9da1-5c582d400243
                © The Author(s) 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 1 November 2017
                : 23 March 2018
                Categories
                Review Article
                Custom metadata
                © Springer Nature B.V. 2018

                Geriatric medicine
                cd4 t cells,subset differentiation,influenza,aging
                Geriatric medicine
                cd4 t cells, subset differentiation, influenza, aging

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