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Purification and Expansion of Mouse Invariant Natural Killer T Cells for in vitro and in vivo Studies
Published on: February 15, 2021
Invariant natural killer (iNK) T cell deficiency in patients with common variable immunodeficiency
D A Fulcher1, D T Avery, N L Fewings
1Immunology Unit, Institute of Clinical Pathology and Medical Research, Westmead Hospital, Westmead, Sydney, NSW 2145, Australia. david_fulcher@wmi.usyd.edu.au
Insights
Common variable immunodeficiency (CVID) involves impaired B cell development. This study found fewer invariant NK (iNK) T cells in CVID patients, potentially linking iNK T cell deficiency to reduced antibody production.
Area of Science:
- Immunology
- Cellular Biology
- Clinical Medicine
Background:
- Common variable immunodeficiency (CVID) is a primary B cell immunodeficiency characterized by impaired antibody production.
- A definitive cellular pathogenesis for CVID remains elusive.
- Invariant NK (iNK) T cells play crucial immunoregulatory roles and are absent in certain immunodeficiencies.
Purpose of the Study:
- To investigate the proportion of iNK T cells in patients with CVID.
- To explore the potential relationship between iNK T cell numbers and CVID pathogenesis, specifically memory B cell development and antibody secretion.
Main Methods:
- Quantification of iNK T cells in the peripheral blood of 58 CVID patients and control groups.
- Subset analysis of iNK T cells based on clinical features and memory B cell levels.
Main Results:
- A significant reduction in the proportion of iNK T cells was observed in CVID patients compared to controls.
- This decrease was particularly pronounced in CVID patients with low isotype-switched memory B cells.
- No significant differences in iNK T cell proportions were found when stratified by specific clinical manifestations of CVID.
Conclusions:
- The diminished proportion of iNK T cells in CVID patients suggests a potential link to the underlying pathophysiology.
- Reduced iNK T cell numbers may contribute to the observed failure in memory B cell generation and subsequent impaired antibody production in CVID.
Abstract:
Common variable immunodeficiency (CVID) is a B cell immunodeficiency disorder characterized frequently by failure of memory B cell development and antibody secretion. A unifying cellular pathogenesis for CVID has not been forthcoming, but given the immunoregulatory role of invariant NK (iNK) T cells and their absence in several other immunodeficiencies, we quantified these cells in the blood of 58 CVID patients. There was a marked decrease in the proportion of iNK T cells in CVID patients compared with controls. This was particularly notable in those with low isotype-switched memory B cells, but subset analysis demonstrated no difference when stratified by specific clinical features. We propose that the decreased proportion of iNK T cells in CVID might be linked to the failure of memory B cell generation, which may contribute to reduced antibody production in these patients.
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