University of Minnesota
https://twin-cities.umn.edu/
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Milestone
2.5.b

CD4 and CD8 effector functions

In progress

Determine CD4 or CD8 T-cell effector functions that are most needed to enhance protective immunity or to modulate disease severity and determine whether T cells require localization in lymph nodes or mucosal tissue to be protective, and characterize the drivers and markers of T-cell homing to the respiratory mucosa.

Progress Highlights

Schattgen 2024 profiled blood and draining lymph node samples from human volunteers for over 2 years after two influenza vaccines were administered 1 year apart to define the evolution of the CD4 TFH cell response. They identified several influenza-specific TFH cell clonal lineages, including multiple responses targeting internal influenza virus proteins, and found that each TFH cell state was attainable within a clonal lineage, indicating that human TFH cells form a durable and dynamic multi-tissue network.

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Mettelman 2023 defined baseline immune cell subsets correlated with protection against symptomatic influenza independently from or synergistically with humoral responses and investigated the contributions of baseline cellular and humoral immune responses in mediating protective anti-influenza virus immunity. Results demonstrated that the baseline composition of peripheral cells improved the prediction of influenza susceptibility over serology, vaccination, or demographics alone.

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Lobby 2022 examined the mechanisms driving enhancement of TRM cells in the respiratory tract after immunization with replication-deficient Ad vectors vaccines in a murine model. 

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Zheng 2022 investigated how pre-existing Ab immunity to influenza virus established from prior immunizations affects the development of CD8 T-cell responses evoked after vaccination with an LAIV. Results showed that pre-existing influenza-specific Abs directed against the vaccine backbone attenuate the size and quality of the vaccine-induced CD8 T-cell response, but that increasing the vaccine dose can overcome this impediment, resulting in improved vaccine-induced circulating and tissue-resident memory CD8 T-cell responses, which were protective against heterologous influenza challenge. 

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Paterson 2021 investigated the kinetics, phenotypes, and function of influenza virus-specific CD8 TRM cells in the lower airway. Results indicated that CD8 TRM cells in the human lung display innate-like gene and protein expression, demonstrating blurred divisions between innate and adaptive immunity.

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Thapa 2021 used a mouse co-transfer model to examine how infant T cells generate greater numbers of lung-homing effector cells in response to influenza infection compared with adult T cells in the same host, due to augmented T-cell receptor–mediated signaling.

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