Abstract

Little is known about cell-mediated immune responses to natural influenza infection in solid organ transplant (SOT) patients. The aim of our study was to evaluate the CD4+ and CD8+ responses to influenza A and B infection in a cohort of SOT patients. We collected peripheral blood mononuclear cells at influenza diagnosis and four weeks later from 31 SOT patients during the 2017–2018 influenza season. Infection-elicited influenza-specific CD4+ and CD8+ T-cell responses were measured using flow cytometry and intracellular cytokine staining and compared to responses following influenza vaccine in SOT patients. Natural infection was associated with a significant increase in CD4+ T-cell responses. For example, polyfunctional cells increased from 21 to 782 and from 193 to 1436 cells per 106 CD4+ T-cells among influenza A/H3N2 and B-infected patients (p = 0.006 and 0.004 respectively). Moreover, infection-elicited CD4+ responses were superior than vaccine-elicited responses for influenza A/H1N1 (931 vs 1; p = 0.026), A/H3N2 (647 vs 1; p = 0.041) and B (619 vs 1; p = 0.004). Natural influenza infection triggers a significant increase in CD4+ T-cell responses in SOT patients. Infection elicits significantly stronger CD4+ responses compared to the influenza vaccine and thereby likely elicits better protection against reinfection.

Highlights

  • Solid organ transplant (SOT) recipients are at increased risk for morbidity and mortality following influenza virus infection because of lifelong immunosuppression required to avoid graft rejection[1,2]

  • We evaluated the dynamics of influenza-specific cell-mediated immunity in a cohort of solid organ transplant (SOT) patients infected with influenza and compared T-cell responses to a cohort of vaccinated patients

  • Our study shows that influenza infection elicited T-cell responses primarily for CD4+. These responses appear to be cross-reactive with other influenza strains

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Summary

Introduction

Solid organ transplant (SOT) recipients are at increased risk for morbidity and mortality following influenza virus infection because of lifelong immunosuppression required to avoid graft rejection[1,2]. The humoral arm is responsible for production of neutralizing antibodies, support antibody-dependent cellular cytotoxicity, opsonization and complement fixation, whereas the cellular arm allows for direct killing of the pathogen and assists in the production of neutralizing antibodies[8] Both arms are important in the immune response against natural influenza infection[8], and it is unclear whether the development of cellular or humoral immunity is a better correlate of protection against subsequent infection. Most of the data available about the development of immunity against natural influenza infection are focused on the antibody responses This is most likely related to the fact that measurement of humoral immunity is significantly less labour-intensive, there is standardization of assays and a better consensus on cut-off values required for protection. P-value evaluate the CD4 + and CD8 + T-cell responses during natural influenza infection in a cohort of SOT patients and to compare it to the T-cell responses elicited by the influenza vaccine in this population

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