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Effect of immunosuppression on T-helper 2 and B-cell responses to influenza vaccination


Egli, Adrian; Humar, Atul; Widmer, Lukas A; Lisboa, Luiz F; Santer, Deanna M; Mueller, Thomas; Stelling, Joerg; Baluch, Aliyah; O'Shea, Daire; Houghton, Michael; Kumar, Deepali (2015). Effect of immunosuppression on T-helper 2 and B-cell responses to influenza vaccination. Journal of Infectious Diseases, 212(1):137-146.

Abstract

BACKGROUND: Influenza vaccine immunogenicity is suboptimal in immunocompromised patients. However, there are limited data on the interplay of T- and B- cell responses to vaccination with simultaneous immunosuppression.
METHODS: We collected peripheral blood mononuclear cells from transplant recipients before and 1 month after seasonal influenza vaccination. Before and after vaccination, H1N1-specific T- and B-cell activation were quantified with flow cytometry. We also developed a mathematical model using T- and B-cell markers and mycophenolate mofetil (MMF) dosage.
RESULTS: In the 47 patients analyzed, seroconversion to H1N1 antigen was demonstrated in 34%. H1N1-specific interleukin 4 (IL-4)-producing CD4(+) T-cell frequencies increased significantly after vaccination in 53% of patients. Prevaccine expression of H1N1-induced HLA-DR and CD86 on B cells was high in patients who seroconverted. Seroconversion against H1N1 was strongly associated with HLA-DR expression on B cells, which was dependent on the increase between prevaccine and postvaccine H1N1-specific IL-4(+)CD4(+) T cells (R(2) = 0.35). High doses of MMF (≥ 2 g/d) led to lower seroconversion rates, smaller increase in H1N1-specific IL-4(+)CD4(+) T cells, and reduced HLA-DR expression on B cells. The mathematical model incorporating a MMF-inhibited positive feedback loop between H1N1-specific IL-4(+)CD4(+) T cells and HLA-DR expression on B cells captured seroconversion with high specificity.
CONCLUSIONS: Seroconversion is associated with influenza-specific T-helper 2 and B-cell activation and seems to be modulated by MMF.

Abstract

BACKGROUND: Influenza vaccine immunogenicity is suboptimal in immunocompromised patients. However, there are limited data on the interplay of T- and B- cell responses to vaccination with simultaneous immunosuppression.
METHODS: We collected peripheral blood mononuclear cells from transplant recipients before and 1 month after seasonal influenza vaccination. Before and after vaccination, H1N1-specific T- and B-cell activation were quantified with flow cytometry. We also developed a mathematical model using T- and B-cell markers and mycophenolate mofetil (MMF) dosage.
RESULTS: In the 47 patients analyzed, seroconversion to H1N1 antigen was demonstrated in 34%. H1N1-specific interleukin 4 (IL-4)-producing CD4(+) T-cell frequencies increased significantly after vaccination in 53% of patients. Prevaccine expression of H1N1-induced HLA-DR and CD86 on B cells was high in patients who seroconverted. Seroconversion against H1N1 was strongly associated with HLA-DR expression on B cells, which was dependent on the increase between prevaccine and postvaccine H1N1-specific IL-4(+)CD4(+) T cells (R(2) = 0.35). High doses of MMF (≥ 2 g/d) led to lower seroconversion rates, smaller increase in H1N1-specific IL-4(+)CD4(+) T cells, and reduced HLA-DR expression on B cells. The mathematical model incorporating a MMF-inhibited positive feedback loop between H1N1-specific IL-4(+)CD4(+) T cells and HLA-DR expression on B cells captured seroconversion with high specificity.
CONCLUSIONS: Seroconversion is associated with influenza-specific T-helper 2 and B-cell activation and seems to be modulated by MMF.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Nephrology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:1 July 2015
Deposited On:05 Feb 2016 13:33
Last Modified:05 Apr 2016 20:06
Publisher:Oxford University Press
ISSN:0022-1899
Additional Information:This is a pre-copy-editing, author-produced PDF of an article accepted for publication in the Journal of Infectious Diseases following peer review. The definitive publisher-authenticated version J Infect Dis. (2015) 212 (1): 137-146. is available online at: http://jid.oxfordjournals.org/content/212/1/137.
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1093/infdis/jiv015
PubMed ID:25589334

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