Aberrant expression of costimulatory molecules in splenocytes of the mevalonate kinase‐deficient mouse model of human hyper‐IgD syndrome (HIDS)

Elizabeth J Hager; Jon D Piganelli; Hubert M Tse; K. Michael Gibson

doi:10.1007/s10545-011-9349-x

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Aberrant expression of costimulatory molecules in splenocytes of the mevalonate kinase‐deficient mouse model of human hyper‐IgD syndrome (HIDS)

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Aberrant expression of costimulatory molecules in splenocytes of the mevalonate kinase‐deficient mouse model of human hyper‐IgD syndrome (HIDS)

Elizabeth J Hager, Jon D Piganelli, Hubert M Tse and K. Michael Gibson

Journal of inherited metabolic disease, Vol.35(1), pp.159-168

01/2012

DOI: https://doi.org/10.1007/s10545-011-9349-x

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https://hdl.handle.net/2376/105705

PMCID: PMC3654530

PMID: 21607759

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Abstract

Objective We sought to determine the activation status and proliferative capacities of splenic lymphocyte populations from a mevalonate kinase‐deficient mouse model of hyper‐IgD syndrome (HIDS). We previously reported that murine mevalonate kinase gene ablation was embryonic lethal for homozygous mutants while heterozygotes (Mvk+/−) demonstrated several phenotypic features of human HIDS including increased serum levels of IgD, IgA, and TNFα, temperature dysregulation, hematological abnormalities, and splenomegaly. Methods and results Flow cytometric analysis of cell surface activation markers on T and B lymphocytes, and macrophage populations, demonstrated aberrant expression of B7 glycoproteins in all splenic cell types studied. Differences in expression levels between Mvk+/− and Mvk+/+ littermate controls were observed in both the basal state (unstimulated) and after Concanavalin A (Con‐A) stimulation in vitro of whole splenocyte cultures. In Mvk+/− CD4 and CD8 T cells, alterations in expression of CD25, CD80, CD152, and CD28 were observed. Mvk+/− splenic macrophages expressed altered levels of CD80, CD86, CD40, and CD11c while Mvk+/− B lymphocytes had differential expression of CD40, CD80, and CD86. Mvk+/− splenocyte subpopulations also exhibited altered proliferative capacities in response to in vitro stimulation. Conclusion We postulate that imbalances in the expression of cell surface proteins necessary for activation, proliferation, and regulation of the intensity and duration of an immune response may result in defective T cell activation, proliferation, and effector functions in our model and potentially in human HIDS.

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Title: Aberrant expression of costimulatory molecules in splenocytes of the mevalonate kinase‐deficient mouse model of human hyper‐IgD syndrome (HIDS)
Creators: Elizabeth J Hager - Biological Testing Branch, National Cancer Institute, Fairview Center Suite, 205
Jon D Piganelli - University of Pittsburgh School of Medicine
Hubert M Tse - University of Alabama at Birmingham
K. Michael Gibson - Michigan Technological University
Publication Details: Journal of inherited metabolic disease, Vol.35(1), pp.159-168
Academic Unit: Pharmacotherapy, Department of
Publisher: Springer Netherlands; Dordrecht
Number of pages: 10
Identifiers: 99900546612301842
Language: English
Resource Type: Journal article