Abstract
The contribution of the decline in thymic activity for the emergence of autoimmunity is still debatable. Immune-competent adults submitted to complete thymectomy early in life provide a unique model to address this question. We applied here strict criteria to identify adults lacking thymic activity based on sjTREC levels, to exclude thymic rebound and/or ectopic thymuses. In agreement, they featured severe naïve CD4 T-cell depletion and contraction of T-cell receptor diversity. Notwithstanding this, there was neither increased incidence of autoimmune disease in comparison with age-matched controls nor significant changes in their IgG/IgA/IgM/IgE autoreactivity profiles, as assessed through extensive arrays. We reasoned that the observed relative preservation of the regulatory T-cell compartment, including maintenance of naïve regulatory CD4 T-cells, may contribute to limit the emergence of autoimmunity upon thymectomy. Our findings have implications in other clinical settings with impaired thymic activity, and are particularly relevant to studies of autoimmunity in ageing.
MeSH terms
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Adult
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Aging / immunology*
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Autoimmune Diseases / prevention & control
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CD4 Lymphocyte Count
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CD4-Positive T-Lymphocytes / cytology
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CD4-Positive T-Lymphocytes / immunology
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Female
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Gene Expression
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Humans
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Hypersensitivity / prevention & control
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Immunocompetence*
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Immunoglobulin Isotypes / biosynthesis*
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Immunoglobulin Isotypes / genetics
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Infant
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Longitudinal Studies
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Male
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Receptors, Antigen, T-Cell / deficiency
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Receptors, Antigen, T-Cell / genetics
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Receptors, Antigen, T-Cell / immunology
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T-Lymphocytes, Regulatory / cytology
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T-Lymphocytes, Regulatory / immunology*
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Thymectomy / rehabilitation*
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Thymus Gland / immunology
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Thymus Gland / surgery*
Substances
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Immunoglobulin Isotypes
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Receptors, Antigen, T-Cell
Grants and funding
This work was supported by Fundação para a Ciência e Tecnologia (FCT; POCI2010/IC/83068/2007 to RMMV; PTDC/SAU-MIC/109786/2009 to AES), and Gulbenkian Foundation (P132532/2013 to AES). SLS, ASA and AJA received FCT scholarships. AJA was supported by an EMBO long-term fellowship (ALT-33-2010) and a Marie Curie European Integration Grant (PERG-GA-2009-256595).