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Rectification of age-associated deficiency in cytotoxic T cell response

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  • Rectification of age-associated deficiency in cytotoxic T cell response

    J Immunol. 2007 Nov 1;179(9):6153-9
    Rectification of age-associated deficiency in cytotoxic T cell response to influenza a virus by immunization with immune complexes.<?xml:namespace prefix = o ns = "urn:schemas-microsoft-com:office:office" /><o:p></o:p>

    http://www.ncbi.nlm.nih.gov/sites/en...t=AbstractPlus<o:p></o:p>

    Zheng B, Zhang Y, He H, Marinova E, Switzer K, Wansley D, Mbawuike I, Han S.<o:p></o:p>
    Department of Immunology.<o:p></o:p>
    Decline in cellular immunity in aging compromises protection against infectious diseases and leads to the increased susceptibility of the elderly to infection. In particular, Ag-specific cytotoxic T lymphocyte (CTL) response against virus is markedly reduced in an aged immune system. It is of great importance to explore novel strategy in eliciting effective antiviral CTL activity in the elderly. In this study, the efficacy and mechanisms of immunization with immune complexes in overcoming age-associated deficiency in cellular immunity were investigated. In this study, we show that the severely depressed CTL response to influenza A in aged mice can be significantly restored by immunization with immune complexes consisting of influenza A virus and mAb to influenza A nucleoprotein. The main mechanisms underlying this recovery of CTL response induced by immune complex immunization in aged mice are enhanced dendritic cell function and elevated production of IFN-gamma in both CD4(+) Th1 and CD8(+) CTLs. Thus, these results demonstrate that immune complex immunization may represent a novel strategy to elicit effective virus-specific cytotoxic response in an aged immune system, and possibly, to overcome age-related immune deficiency in general.<o:p></o:p>
    PMID: 17947690 [PubMed - in process]<o:p></o:p>
    <o:p></o:p>
    Last edited by AlaskaDenise; November 2, 2007, 06:20 PM. Reason: fix hyperlink to article

  • #2
    Re: Rectification of age-associated deficiency in cytotoxic T cell response

    a related 2004 paper referenced in the "related links"....

    <DT class=head><INPUT id=UidCheckBox type=checkbox value=15004143 name=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPa nel.Pubmed_RVAbstractPlus.uid sid="1">1: J Immunol. 2004 Mar 15;172(6):3437-46.
    </DT><DT class=head>
    </DT><DT class=head>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.
    </DT><DT class=head>
    </DT><DD class=abstract><!--AuthorList-->Deng Y, Jing Y, Campbell AE, Gravenstein S.
    Glennan Center for Geriatrics and Gerontology, Department of Internal Medicine, Eastern Virginia Medical School, Norfolk, VA 23507, USA. dengy@evms.edu
    </DD><DD class=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.
    </DD><DD class=abstract>
    </DD><DD class=abstract>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.
    </DD><DD class=abstract>
    </DD><DD class=abstract>The reduced frequency of IFN-gamma+ ISMT was accompanied by a reduced level of IFN-gamma secretion per cell in elderly subjects.
    </DD><DD class=abstract>
    </DD><DD class=abstract>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.
    </DD><DD class=abstract>
    </DD><DD class=abstract>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.
    </DD><DD class=abstract>
    </DD><DD class=abstract>The expansion of influenza-specific CD8+ T cells in CTL cultures was reduced in the elderly.
    </DD><DD class=abstract>
    </DD><DD class=abstract>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.
    </DD><DD class=abstract>
    </DD><DD class=abstract>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.
    </DD><DD class=abstract>
    PMID: 15004143 [PubMed - indexed for MEDLINE]
    </DD>
    "The next major advancement in the health of American people will be determined by what the individual is willing to do for himself"-- John Knowles, Former President of the Rockefeller Foundation

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    • #3
      Re: Rectification of age-associated deficiency in cytotoxic T cell response

      This is not surprising and is consistent with the fact that there is a general decline in cell functions with age, less effective vaccination in elderly people and so on.

      I can`t see that these findings will lead to a new therapeutic concept taken the common risks of circulating immune complexes.

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