Differential immunomodulation of T-cells by immunoglobulin replacement therapy in primary and secondary antibody deficiency


Autoři: Tri Dinh aff001;  Jun Oh aff001;  Donald William Cameron aff002;  Seung-Hwan Lee aff001;  Juthaporn Cowan aff001
Působiště autorů: Department of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada aff001;  Division of Infectious Diseases, Department of Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada aff002;  Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada aff003
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article
doi: 10.1371/journal.pone.0223861

Souhrn

Patients with primary or secondary antibody deficiency (PAD or SAD) are at increased risk of recurrent infections that can be alleviated by immunoglobulin replacement therapy (IRT). In addition to replenishing antibody levels, IRT has been suggested to modulate immune response in patients with antibody deficiency. Although both commonly treated with IRT, the underlying causes of PAD and SAD vary greatly, suggesting differential modulation of T-cell function that may lead to different responses to IRT. To explore this, peripheral blood mononuclear cells (PBMCs) were sampled from 17 PAD and 14 SAD patients before and 2–10 months after initiation of IRT, and analyzed for changes in T-cell phenotype and function. Proportions of CD4, CD8, Treg, or memory T-cells did not significantly change post-IRT compared to pre-IRT. However, we report distinct modulation in T-cell function between PAD and SAD patients post-IRT. Upon α-CD3/CD28 stimulation, proportion of IFN-γ+ CD4 and CD8 T-cells increased in SAD (p = 0.005) but not PAD patients post-IRT compared to baseline. Interestingly, total T-cell proliferation was reduced post-IRT in both PAD and SAD patients, although the reduction in proliferation was primarily due to reduced CD4 T-cell proliferation in PAD (p = 0.025) in contrast to CD8 T-cells in SAD (p = 0.042). In summary, even though IRT provides patients with passive humoral immunity-mediated protection in PAD and SAD, our findings suggest that IRT immunomodulation of T-cells is different in T-cell subsets depending on underlying immunodeficiency.

Klíčová slova:

Antibodies – Blood – Cytokines – Cytotoxic T cells – Flow cytometry – Memory T cells – T cells – Immune deficiency


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