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Age-related impaired type 1 T cell responses to influenza: reduced activation ex vivo, decreased expansion in CTL culture in vitro, and blunted response to influenza vaccination in vivo in the elderly.

Abstract

The objective of this study was to analyze the changes in the type 1 T cell response, including the CD4+ Th1 and CD8+ T cell responses, to influenza in the elderly compared with those in young adults. PBMC activated ex vivo with influenza virus exhibited an age-related decline in type 1 T cell response, shown by the decline in the frequency of IFN-gamma-secreting memory T cells specific for influenza (IFN-gamma+ ISMT) using ELISPOT or intracellular cytokine staining. The reduced frequency of IFN-gamma+ ISMT was accompanied by a reduced level of IFN-gamma secretion per cell in elderly subjects. Tetramer staining, combined with IFN-gamma ELISPOT, indicated that the decline in IFN-gamma+, influenza M1-peptide-specific T cells was not due to attrition of the T cell repertoire, but, rather, to the functional loss of ISMT with age. In addition, the decline in type 1 T cell response was not due to an increase in Th2 response or defects in APCs from the elderly. The expansion of influenza-specific CD8+ T cells in CTL cultures was reduced in the elderly. Compared with young subjects, frail elderly subjects also exhibited a blunted and somewhat delayed type 1 T cell response to influenza vaccination, which correlated positively with the reduced IgG1 subtype and the total Ab response. Taken together, these data demonstrate that there is a decline in the type 1 T cell response to influenza with age that may help explain the age-related decline in vaccine efficacy and the increases in influenza morbidity and mortality.

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  • Authors+Show Affiliations

    ,

    Glennan Center for Geriatrics and Gerontology, Department of Internal Medicine, Eastern Virginia Medical School, Norfolk, VA 23507, USA. dengy@evms.edu

    , ,

    Source

    MeSH

    Adult
    Aged
    Aged, 80 and over
    Aging
    Antibodies, Viral
    Cell Division
    Cells, Cultured
    Cytokines
    Enzyme-Linked Immunosorbent Assay
    Epitopes, T-Lymphocyte
    Flow Cytometry
    Frail Elderly
    Herpesvirus 3, Human
    Humans
    Influenza A virus
    Influenza Vaccines
    Interferon-gamma
    Leukocytes, Mononuclear
    Lymphocyte Activation
    Middle Aged
    Th1 Cells
    Th2 Cells
    Viral Matrix Proteins

    Pub Type(s)

    Comparative Study
    Journal Article
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

    Language

    eng

    PubMed ID

    15004143

    Citation

    Deng, Yuping, et al. "Age-related Impaired Type 1 T Cell Responses to Influenza: Reduced Activation Ex Vivo, Decreased Expansion in CTL Culture in Vitro, and Blunted Response to Influenza Vaccination in Vivo in the Elderly." Journal of Immunology (Baltimore, Md. : 1950), vol. 172, no. 6, 2004, pp. 3437-46.
    Deng Y, Jing Y, Campbell AE, et al. Age-related impaired type 1 T cell responses to influenza: reduced activation ex vivo, decreased expansion in CTL culture in vitro, and blunted response to influenza vaccination in vivo in the elderly. J Immunol. 2004;172(6):3437-46.
    Deng, Y., Jing, Y., Campbell, A. E., & Gravenstein, S. (2004). Age-related impaired type 1 T cell responses to influenza: reduced activation ex vivo, decreased expansion in CTL culture in vitro, and blunted response to influenza vaccination in vivo in the elderly. Journal of Immunology (Baltimore, Md. : 1950), 172(6), pp. 3437-46.
    Deng Y, et al. Age-related Impaired Type 1 T Cell Responses to Influenza: Reduced Activation Ex Vivo, Decreased Expansion in CTL Culture in Vitro, and Blunted Response to Influenza Vaccination in Vivo in the Elderly. J Immunol. 2004 Mar 15;172(6):3437-46. PubMed PMID: 15004143.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Age-related impaired type 1 T cell responses to influenza: reduced activation ex vivo, decreased expansion in CTL culture in vitro, and blunted response to influenza vaccination in vivo in the elderly. AU - Deng,Yuping, AU - Jing,Yu, AU - Campbell,Ann E, AU - Gravenstein,Stefan, PY - 2004/3/9/pubmed PY - 2004/7/14/medline PY - 2004/3/9/entrez SP - 3437 EP - 46 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J. Immunol. VL - 172 IS - 6 N2 - The objective of this study was to analyze the changes in the type 1 T cell response, including the CD4+ Th1 and CD8+ T cell responses, to influenza in the elderly compared with those in young adults. PBMC activated ex vivo with influenza virus exhibited an age-related decline in type 1 T cell response, shown by the decline in the frequency of IFN-gamma-secreting memory T cells specific for influenza (IFN-gamma+ ISMT) using ELISPOT or intracellular cytokine staining. The reduced frequency of IFN-gamma+ ISMT was accompanied by a reduced level of IFN-gamma secretion per cell in elderly subjects. Tetramer staining, combined with IFN-gamma ELISPOT, indicated that the decline in IFN-gamma+, influenza M1-peptide-specific T cells was not due to attrition of the T cell repertoire, but, rather, to the functional loss of ISMT with age. In addition, the decline in type 1 T cell response was not due to an increase in Th2 response or defects in APCs from the elderly. The expansion of influenza-specific CD8+ T cells in CTL cultures was reduced in the elderly. Compared with young subjects, frail elderly subjects also exhibited a blunted and somewhat delayed type 1 T cell response to influenza vaccination, which correlated positively with the reduced IgG1 subtype and the total Ab response. Taken together, these data demonstrate that there is a decline in the type 1 T cell response to influenza with age that may help explain the age-related decline in vaccine efficacy and the increases in influenza morbidity and mortality. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/15004143/Age_related_impaired_type_1_T_cell_responses_to_influenza:_reduced_activation_ex_vivo_decreased_expansion_in_CTL_culture_in_vitro_and_blunted_response_to_influenza_vaccination_in_vivo_in_the_elderly_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=15004143 DB - PRIME DP - Unbound Medicine ER -