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Influenza A, B and C viruses (IAV, IBV and ICV, respectively) circulate globally and infect humans, with IAV and IBV causing the most severe disease. CD8+T cells confer cross-protection against IAV strains, however the responses of CD8+T cells to IBV and ICV are understudied. We investigated the breadth of CD8+T cell cross-recognition and provide evidence of CD8+T cell cross-reactivity across IAV, IBV and ICV. We identified immunodominant CD8+T cell epitopes from IBVs that were protective in mice and found memory CD8+T cells directed against universal and influenza-virus-type-specific epitopes in the blood and lungs of healthy humans. Lung-derived CD8+T cells displayed tissue-resident memory phenotypes. Notably, CD38+Ki67+CD8+effector T cells directed against novel epitopes were readily detected in IAV- or IBV-infected pediatric and adult subjects. Our study introduces a new paradigm whereby CD8+T cells confer unprecedented cross-reactivity across all influenza viruses, a key finding for the design of universal vaccines.

We hypothesized that a reduced potential for bronchiolar stem-cell (Clara cell)–related repair in the setting of an ever-present risk of small airway injury would increase the risk of bronchiolitis obliterans syndrome (BOS).

Mannose-binding lectin (MBL) is a key molecule of the innate immune system and, in addition to the classical and alternative pathways, a principle driver of complement activation. Genetic mutations of MBL are common, result in low serum levels of MBL, and are associated with increased infection risk in solid-organ transplant recipients.

Cross-reactive antiviral memory T cells constitute a significant proportion of the alloresponse, potentially playing a pivotal role in adverse posttransplant outcomes in human leukocyte antigen (HLA)-mismatched allografts. We explored the longitudinal dynamics of cross-reactive HLA-B8-restricted Epstein-Barr virus-specific CD8T cells directed toward the EBNA3A epitope FLRGRAYGL (FLR) in lung transplant recipients (LTRs) to determine whether their corecognition of HLA-B4402 expressed on the allograft contributed to poorer posttransplant outcomes.

In addition to their known antiviral and host defense functions, emerging evidence suggests that natural killer (NK) cells may influence allograft outcomes after solid organ transplantation. Although it is accepted that NK cells are activated in the absence of self-major histocompatibility complex (MHC) class I molecules, little is known of how NK cell dynamics change after transplantation of a MHC disparate lung allograft.

Everolimus has recently shown promise in terms of short- and long-term clinical lung transplant outcomes. This study aims to determine the altered lung allograft cellular and cytokine mileau when everolimus is substituted for azathioprine (AZA). Twenty-three stable lung transplantation (LTx) recipients were randomized in a double-blinded study to receive everolimus (13) or AZA (10) plus standard cyclosporine/prednisolone. Bronchoalveolar lavage (BAL) and endobronchial biopsies (EBB) were performed on three occasions (T0–T2) to elucidate cellular and cytokine profiles via immunocytochemistry, immunohistology and enzyme-linked immunosorbent assay (ELISA) techniques. There were no group differences for demographics or clinical events throughout the study nor baseline cellular/cytokine differences. BAL lymphocyte percentage fell in the AZA group by T2 (p = 0.05). BAL and EBB CD4 measures significantly declined in the everolimus group by T2 (p < 0.05). EBB neutrophils rose significantly in the AZA group, with a fall in the everolimus group resulting in a significant difference at T2 (p = 0.01). In conclusion, everolimus has contributed to potentially important differences in BAL and EBB cellular profiles.

Everolimus has recently shown promise in terms of short- and long-term clinical lung transplant outcomes. This study aims to determine the altered lung allograft cellular and cytokine mileau when everolimus is substituted for azathioprine (AZA). Twenty-three stable lung transplantation (LTx) recipients were randomized in a double-blinded study to receive everolimus (13) or AZA (10) plus standard cyclosporine/prednisolone. Bronchoalveolar lavage (BAL) and endobronchial biopsies (EBB) were performed on three occasions (T0–T2)to elucidate cellular and cytokine profiles via immunocytochemistry, immunohistology and enzyme-linked immunosorbent assay (ELISA) techniques. There were no group differences for demographics or clinical events throughout the study nor baseline cellular/cytokine differences. BAL lymphocyte percentage fell in the AZA group by T2(p = 0.05). BAL and EBB CD4 measures significantly declined in the everolimus group by T2(p < 0.05).EBB neutrophils rose significantly in the AZA group, with a fall in the everolimus group resulting in a significant difference at T2(p = 0.01). In conclusion, everolimus has contributed to potentially important differences in BAL and EBB cellular profiles.

Liberalization of tobacco exposure history as an exclusion to lung donation has recently occurred to increase donor organ availability. This study investigated the effect of donor smoking status and current and cumulative cigarette dose on early and late outcomes in lung transplantation.

Posttransplant lymphoproliferative disease (PTLD) in lung transplant recipients (LTRs) is potentially lethal with considerable morbidity. The role of donor (D)/recipient (R) HLA matching is unknown.

SARS-CoV-2 causes a spectrum of COVID-19 disease, the immunological basis of which remains ill defined. We analyzed 85 SARS-CoV-2-infected individuals at acute and/or convalescent time points, up to 102 days after symptom onset, quantifying 184 immunological parameters. Acute COVID-19 presented with high levels of IL-6, IL-18, and IL-10 and broad activation marked by the upregulation of CD38 on innate and adaptive lymphocytes and myeloid cells. Importantly, activated CXCR3+cTFH1 cells in acute COVID-19 significantly correlate with and predict antibody levels and their avidity at convalescence as well as acute neutralization activity. Strikingly, intensive care unit (ICU) patients with severe COVID-19 display higher levels of soluble IL-6, IL-6R, and IL-18, and hyperactivation of innate, adaptive, and myeloid compartments than patients with moderate disease. Our analyses provide a comprehensive map of longitudinal immunological responses in COVID-19 patients and integrate key cellular pathways of complex immune networks underpinning severe COVID-19, providing important insights into potential biomarkers and immunotherapies.