Abstract

Interventions for influenza virus infections are essential to minimize the worldwide annual morbidity, mortality, and economic loss caused by this highly contagious respiratory pathogen. Establishment of universal, long-lasting protection against epidemic and pandemic strains of the virus can potentially eradicate the necessity of annual reformulation and readministration of low-efficacious seasonal vaccines, increasing pandemic preparedness. The protective potential of Type 1 T helper (TH1)-polarized memory CD4+ T cells against Influenza A virus (IAV) infection and generation of secondary memory populations following viral clearance are well-characterized. To assess the potential of CD4+ T memory cells as a candidate for adoptive immunotherapy, here we validated and optimized cryopreserved IAV-specific memory CD4+ T cell-mediated protection against infection and evaluated their potential for subsequent memory formation. Donor-derived in vitro-generated memory CD4+ T cells were transferred into IAV-infected naïve mice following cryopreservation of these cells for 6-12 months and overnight activation with gamma-chain cytokines, interleukin (IL)-7 and IL-7+IL-2. Results showed that cytokine-cultured cryopreserved memory CD4+ T cells, compared to their non-cultured counterparts, controlled viral titer in the lung at the peak infection phase, decreased morbidity, expedited recovery, and formed increased secondary memory cells in the lung, the primary site of infection, including lung tissue-resident memory (TRM) CD4+ T cells. Phenotypic and functional analysis confirmed that donor-derived secondary memory CD4+ T cells retain a TH1-phenotype and produce cytokines associated with protection against IAV. These observations support that the protectiveness and memory-forming potential of host- and/or donor-derived memory CD4? T cells can be preserved and harnessed for future use. This T-cell based adoptive immunotherapy addresses some of the current challenges of available preventative and therapeutic options, such as low vaccine efficacy, availability of only early treatment drugs, lack of immunity against pandemic strains and effective memory cell generation.

Notes

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Graduation Date

2020

Semester

Summer

Advisor

Strutt, Tara

Degree

Master of Science (M.S.)

College

College of Medicine

Department

Burnett School of Biomedical Sciences

Degree Program

Biotechnology

Format

application/pdf

Identifier

CFE0008570; DP0024246

URL

https://purls.library.ucf.edu/go/DP0024246

Language

English

Release Date

February 2026

Length of Campus-only Access

5 years

Access Status

Masters Thesis (Campus-only Access)

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Restricted to the UCF community until February 2026; it will then be open access.

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