title: Cytomegalovirus Seropositivity Predicts a Decline in the T Cell But Not the Antibody Response to Influenza in Vaccinated Older Adults Independent of Type 2 Diabetes Status.
abstract: Type 2 diabetes mellitus (T2DM) and persistent cytomegalovirus (CMV) infection are postulated contributors to inflammatory processes that impact on the age-related decline in T-cell responses to influenza vaccination. Older subjects with T2DM (n = 30) and healthy aged controls (n = 40) were enrolled and received influenza vaccination in this study. Serum inflammatory markers and CMV serostatus were measured. Pre- to post-vaccination changes in serum antibody titers to the A/H3N2 strain, and levels of granzyme B (GrB, cytotoxic T lymphocytes) in lysates and cytokines in supernatants from influenza A/H3N2-challenged peripheral blood mononuclear cells were measured. We found no difference between the T2DM and healthy groups in the immune responses measured. However, CMV serostatus was a key determinant of the GrB response to influenza challenge; CMV+ subjects had low levels of inducible GrB (iGrB) activity in response to influenza challenge. In contrast, the serum antibody response to the A/H3N2 vaccine strain did not differ with CMV serostatus, and serum levels of the inflammatory marker, β2-microglobulin, were positively correlated with age, T2DM, and serum IL-10 levels. In conclusion, CMV seropositivity associated with a decline in GrB responses to influenza may predict increased susceptibility to influenza in older adults.
authors: Health Sciences North Research Institute, Sudbury, ON, Canada.
authors: Kamran
authors: K
authors: Haq
authors: Research Center on Aging, Université de Sherbrooke, Sherbrooke, QC, Canada.
authors: Tamas
authors: T
authors: Fulop
authors: Department of Medicine, University of British Columbia, Vancouver, Canada.
authors: Gale
authors: G
authors: Tedder
authors: Health Sciences North Research Institute, Sudbury, ON, Canada.
authors: Beth
authors: B
authors: Gentleman
authors: Research Center on Aging, Université de Sherbrooke, Sherbrooke, QC, Canada.
authors: Hugo
authors: H
authors: Garneau
authors: Department of Medicine, University of British Columbia, Vancouver, Canada.
authors: Graydon S
authors: GS
authors: Meneilly
authors: University of Connecticut Center on Aging, Farmington.
authors: Alison
authors: A
authors: Kleppinger
authors: Second Department of Internal Medicine, University of Tübingen Medical School, Tübingen, Germany.|School of Science and Technology, College of Arts and Science, Nottingham Trent University, Nottingham, UK.
authors: Graham
authors: G
authors: Pawelec
authors: Health Sciences North Research Institute, Sudbury, ON, Canada.|University of Connecticut Center on Aging, Farmington.
authors: Janet E
authors: JE
authors: McElhaney
mesh_terms: D000368:Aged; D000917:Antibody Formation / Q000276:immunology*; D001955:British Columbia; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood; D003586:Cytomegalovirus Infections / Q000276:immunology*; D003924:Diabetes Mellitus, Type 2 / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D053804:Granzymes / Q000097:blood; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D053122:Influenza A Virus, H3N2 Subtype; D007252:Influenza Vaccines / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control; D008297:Male; D011237:Predictive Value of Tests; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D016207:Cytokines; D007252:Influenza Vaccines; D053804:Granzymes
keywords: Cytomegalovirus (CMV); Granzyme B; Influenza vaccination; Older adults; T cell