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CVID patients with autoimmunity have elevated T cell expression of granzyme B and HLA-DR and reduced levels of Treg cells
  1. Clive R D Carter1,
  2. Ganesha Aravind2,
  3. Natuley L Smalle1,
  4. June Y Cole1,
  5. Sinisa Savic2,
  6. Philip M D Wood1,2
  1. 1Cellular Immunology Laboratory, Department of Immunology and Transplant Immunology, St James's University Hospital, Leeds, UK
  2. 2Department of Clinical Immunology, Beckett Wing, St James's University Hospital, Leeds, UK
  1. Correspondence to Dr Clive Carter, Cellular Immunology Laboratory, Dept of Immunology and Transplant Immunology, Level 09 Gledhow Wing, St James's University Hospital, Beckett Street, Leeds LS9 7TF, UK; clive.carter{at}leedsth.nhs.uk

Abstract

Aims Common variable immunodeficiency (CVID) is a primary antibody immunodeficiency with approximately 20% of patients reporting additional autoimmune symptoms. The primary aim of this study was to compare the levels of activated and regulatory T cells (Treg cells) in CVID patients in an attempt to clarify their possible interactions leading to the generation of autoimmunity.

Methods Immunophenotyping of T cells was performed by flow cytometry using a whole blood approach. Surface expression of human leukocyte antigen HLA class II DR and intracellular levels of granzyme B in T cell subsets were assessed; Treg levels were measured using CD4 CD25, FOXp3 and CTLA-4.

Results CVID patients had higher levels of granzyme B and HLA-DR on CD8+ T cells compared with control values (mean of 59% vs 30% and 45% vs 21%, respectively). Patients also had reduced levels of Treg cells compared with control values (con mean=3.24% vs pat=2.54%). Patients with autoimmunity (5/23) had a similar level of T cell activation markers to the rest of the patients but with lower Treg cells (mean of 1.1%) and reduced CD25 and CTLA-4 expression. Patients with autoimmunity had a higher ratio of activated to Treg cells compared with patients with no autoimmune symptoms.

Conclusions These results highlight that reduced levels of Treg cells were associated with elevated levels of activated T cells, suggesting that reduced Treg cells in these patients may have functional consequences in allowing exaggerated T cell responses.

  • Immunodeficiency
  • Immunology
  • Immunophenotyping
  • Lymphocytes

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