Discovering the Origins of Immunological Competence

Miller, J. F. A. P.

doi:10.1146/annurev.immunol.17.1.1

Cited by 24 publications

(10 citation statements)

References 50 publications

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“…The thymus, the topic of this article, has interested me since I first heard Jacques Miller discuss his work in 1965 in Brisbane while I was a medical student. Miller is revered for first demonstrating that the thymus produces T cells, but it is often forgotten that he also provided convincing evidence that the thymus is a crucial site for tolerance induction; thus, he showed that strain A T cells arising in a strain B thymus graft displayed skin graft tolerance to B (as well as A) but not to C (1). Proof that thymic tolerance reflects clonal deletion came 25 years later from the crucial studies of the Kappler/Marrack lab on superantigens (2).…”

Section: Prologue (By J Sprent)mentioning

confidence: 99%

The thymus and negative selection

Sprent

Kishimoto

2002

Immunological Reviews

177

126

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Maintenance of tolerance to self antigens is presumed to reflect a combination of central and peripheral tolerance. For T cells, central tolerance occurs during early T cell development in the thymus and causes cells with strong reactivity to self antigens to be destroyed in situ (negative selection). Here, we summarize evidence that negative selection can occur in the thymic medulla and affects a population of semimature HSA+ T cells. The influence of costimulatory molecules, Fas and cytokines on negative selection is discussed.

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Section: Prologue (By J Sprent)mentioning

confidence: 99%

The thymus and negative selection

Sprent

Kishimoto

2002

Immunological Reviews

177

126

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“…Almost half a century ago, a series of neonatal thymectomy experiments in mice performed by Jacques Miller identified the function of the thymus as the generative organ for one of the two major classes of lymphocytes, dubbed accordingly thymus derived or T lymphocytes (1). Since this fundamental discovery, a complex picture of the fascinating process of T‐cell development in the thymus has emerged.…”

Section: Introductionmentioning

confidence: 99%

The role of the transcription factor Foxp3 in the development of regulatory T cells

Kim

Rudensky

2006

Immunological Reviews

161

133

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Early studies of mice subjected to neonatal thymectomy and analyses of adoptive T-cell transfer into lymphopenic hosts led to the identification of a specialized subset of regulatory CD4+ T cells capable of suppressing various manifestations of autoimmunity. Recently, a combination of genetic, molecular, and traditional cellular approaches provided novel powerful means to investigate the biology of these cells. Here, we review earlier and current work from our laboratory, establishing a dedicated function for the transcription factor Foxp3 in the process of regulatory T-cell lineage commitment and a role for TCR- and cytokine-mediated signals in regulation of Foxp3 expression.

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“…The thymus plays a critical role in the development of normal immune tolerance 1. As well as negatively selecting potentially autoreactive T cells, it also positively selects the naturally occurring regulatory T cell subset (T Reg ) (CD4 + FOXP3 + ) 2.…”

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confidence: 99%

Thymic function in juvenile idiopathic arthritis

Lorenzi

Morgan

Anderson

et al. 2008

Annals of the Rheumatic Diseases

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Objective:Thymic function declines exponentially with age. Impaired thymic function has been associated with autoimmune disease in adults but has never been formally assessed in childhood autoimmunity. Therefore, thymic function in children with the autoimmune disease juvenile idiopathic arthritis (JIA) was determined.Methods:Thymic function was measured in 70 children and young adults with JIA (age range 2.1–30.8 (median 10.4)) and 110 healthy age-matched controls using four independent assays. T cell receptor excision circles (WBLogTREC/ml) and the proportion of CD4+ CD45RA+CD31+ T cells (representing recent thymic emigrants; %RTEs) were quantified and intrathymic proliferation measured by calculating the αTREC/ΣβTREC ratio. Lastly, regulatory T cells (TReg) of thymic origin (CD4+FOXP3+) were quantified in peripheral blood to assess the ability of the thymus in JIA to generate this T cell subset.Results:Thymic function was equivalent by all four parameters in JIA when compared with the control population. Furthermore, there was no consistent effect of JIA subtype on thymic function, although intrathymic proliferation was higher in the small rheumatoid factor (RF)+ polyarticular group. There were no significant effects of disease-modifying antirheumatic drugs (DMARDs) or oral corticosteroids on thymic function, although those with the worst prognostic ILAR (International League of Associations for Rheumatology) subtypes were also those most likely to be on a DMARD.Conclusions:It is demonstrated that children and young adults with JIA, unlike adults with autoimmune diseases, have thymic function that is comparable with that of healthy controls. The varied pathologies represented by the term “JIA” suggest this observation may not be disease specific and raises interesting questions about the aetiology of thymic impairment in adult autoimmunity.

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Discovering the Origins of Immunological Competence

Cited by 24 publications

References 50 publications

The thymus and negative selection

The thymus and negative selection

The role of the transcription factor Foxp3 in the development of regulatory T cells

Thymic function in juvenile idiopathic arthritis

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