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

AbstractDeterminants of the acqusition and maintenance of maternal microchimerism (MMc) during infancy and the impact of MMc on infant immune responses are unknown. We examined factors which influence MMc detection and level across infancy and the effect of MMc on T cell responses to BCG vaccination in a cohort of HIV exposed, uninfected and HIV unexposed infants in South Africa. MMc was measured in whole blood from 58 infants using a panel of quantitative PCR assays at day one and 7, 15, and 36 weeks of life. Infants received BCG at birth, and select whole blood samples from infancy were stimulated in vitro with BCG and assessed for polyfunctional CD4+ T cell responses. MMc was present in most infants across infancy at levels ranging from 1-1,193/100,000 genomic equivalents and was positively impacted by absence of maternal HIV, exclusive breastfeeding, and female sex, emphasizing that both maternal and infant factors may shape the maternal graft. Initiation of maternal antiretroviral therapy prior to pregnancy was associated with partial restoration of MMc in HIV exposed, uninfected infants. Birth MMc was associated with an improved polyfunctional CD4+ T cell response to BCG, suggesting that MMc may functionally impact infant immunity.

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CD4 T cell responses to influenza infection

Seminars in Immunology ◽

10.1016/j.smim.2004.02.004 ◽

2004 ◽

Vol 16 (3) ◽

pp. 171-177 ◽

Cited By ~ 113

Author(s):

Deborah M Brown ◽

Eulogia Román ◽

Susan L Swain

Keyword(s):

T Cell ◽

Influenza Infection ◽

T Cell Responses ◽

Cd4 T Cell ◽

Cell Responses

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Differences in Influenza-Specific CD4 T-Cell Mediated Immunity Following Acute Infection Versus Inactivated Vaccination in Children

The Journal of Infectious Diseases ◽

10.1093/infdis/jiaa664 ◽

2020 ◽

Author(s):

Ian Shannon ◽

Chantelle L White ◽

Hongmei Yang ◽

Jennifer L Nayak

Keyword(s):

Early Childhood ◽

T Cell ◽

T Cell Responses ◽

T Cell Response ◽

Cd4 T Cell ◽

Immune Memory ◽

Cell Mediated Immunity ◽

Initial Exposure ◽

Cell Responses ◽

The Impact

Abstract Background Early childhood influenza infections imprint influenza-specific immune memory, with most studies evaluating antibody specificity. In this study, we examined how infection versus inactivated influenza vaccination (IIV) establish pediatric CD4 T-cell mediated immunity to influenza and whether this poises the immune system to respond differently to IIV the following year. Methods We tracked influenza-specific CD4 T-cell responses in 16 H3N2 infected and 28 IIV immunized children following both initial exposure and after cohorts were revaccinated with IIV the following fall. PBMCs were stimulated with peptide pools encompassing the translated regions of the H3 HA and NP proteins and were then stained to assess CD4 T-cell specificity and function. Results Compared to IIV, infection primed a greater magnitude CD4 T-cell response specific for the infecting HA and NP proteins, with more robust NP-specific immunity persisting through year 2. Post infection, CD4 T cells preferentially produced combinations of cytokines that included interferon-γ. Interestingly, age-specific patterns in CD4 T-cell reactivity demonstrated the impact of multiple influenza exposures over time. Conclusions These data indicate that infection and vaccination differentially prime influenza-specific CD4 T-cell responses in early childhood, with these differences contributing to the lasting immunologic imprinting established following early influenza infection. Clinical Trials Registration NCT02559505.

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