Effect of Thymectomy on Human Peripheral Blood T Cell Pools in Myasthenia Gravis

Sempowski, Gregory D.; Thomasch, James R.; Gooding, Maria E.; Hale, Laura P.; Edwards, Lloyd J.; Ciafaloni, Emma; Sanders, Donald B.; Massey, Janice M.; Douek, Daniel C.; Koup, Richard A.; Haynes, Barton F.

doi:10.4049/jimmunol.166.4.2808

Cited by 93 publications

(77 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…4). There is very little solid evidence on the effects of thymectomy on naive T cell numbers in human adults, but there is some evidence supporting the increased loss of TRECs after adult thymectomy (2,45). Thymectomy in young children has a strong impact on the number of naive T cells and their TREC content (46,47).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

The Effects of Age, Thymectomy, and HIV Infection on α and β TCR Excision Circles in Naive T Cells

Dool

Boer

2006

The Journal of Immunology

View full text Add to dashboard Cite

Due to homeostasis total naive T cell numbers remain fairly constant over life despite a gradual involution of the thymus. The contribution of the thymus to maintaining naive T cell pools is typically measured with TCR excision circles (TRECs) that are formed in thymocytes. The mechanisms underlying thymic involution are poorly understood. Some data suggest that thymocytes undergo fewer divisions in old (small) than young (large) thymi, and other data suggest that the number of TRECs per thymocyte is independent of age. If thymic involution were associated with a decreased number of divisions of the thymocytes, this would markedly complicate the interpretation of TREC data. To study this we develop a mathematical model in which the division rate of thymocytes decreases with increasing age. We describe the dilution of TRECs formed during the arrangement of both chains of the TCR by division of thymocytes, recent thymic emigrants, and mature naive T cells. The model behavior is complicated as TREC contents in naive T cells can increase with age due to decreased dilution in the thymus. Because our model is consistent with current data on the effects of age and thymectomy on TRECs in peripheral T cells, we conclude that aging may well affect thymocyte division, which markedly complicates the interpretation of TREC data. It is possible, but more difficult, to let the model be consistent with the rapid changes in α and β TRECs observed shortly after HIV infection.

show abstract

Section: Discussionmentioning

confidence: 99%

“…4), and a rapid loss of RTE can account for a rapid loss of TRECs. However, in the absence of good markers for RTEs, this remains hypothetical, and data from thymectomized monkeys (35) and human adults (45) show little evidence of a biphasic decline in TREC numbers (6) (R. M. Ribeiro and R. J. de Boer, manuscript in preparation).…”

Section: Discussionmentioning

confidence: 99%

The Effects of Age, Thymectomy, and HIV Infection on α and β TCR Excision Circles in Naive T Cells

Dool

Boer

2006

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…Importantly, in late stages of disease, there is no further shortening of telomeres compared with healthy controls, indicating that massive peripheral cell division is not the principal cause for reduced peripheral blood TREC levels. Furthermore, nonthymectomized patients with myasthenia gravis also have declined frequencies of TREC-expressing T cells (30), suggesting that this phenomenon may coincide with autoimmune disorders in general. Altogether, our observations indicate that impaired thymic function rather than an accelerated T cell turnover or Ag-driven expansion of autoaggressive T cell clones is causally related to the pronounced decrease of TREC-expressing T lymphocytes in patients with RRMS.…”

Section: Discussionmentioning

confidence: 99%

Thymic Export Function and T Cell Homeostasis in Patients with Relapsing Remitting Multiple Sclerosis

Hug

Korporal

Schröder

et al. 2003

The Journal of Immunology

132

125

View full text Add to dashboard Cite

Multiple sclerosis (MS) is an inflammatory and possibly autoimmune mediated demyelinating disease of the CNS. Autoimmunity within the CNS may be triggered by dysfunction of peripheral immune tolerance mechanisms via changes in the homeostatic composition of peripheral T cells. We have assessed the release of naive T lymphocytes from the thymus in patients with relapsing remitting MS (RRMS) to identify alterations in the equilibrium of the peripheral T cell compartment. Thymic T cell production was estimated by measuring TCR excision circles (TRECs) as a traceable molecular marker in recent thymic emigrants. A total of 46 treatment-naive patients with active RRMS and 49 gender- and age-matched healthy persons were included in the study. The levels of TREC-expressing CD4+ and CD8+ T lymphocytes were significantly decreased in MS patients, and TREC quantities overall matched those of 30 years older healthy individuals. The average concentrations of TRECs/106 CD4+ and CD8+ T lymphocytes derived from MS patients and healthy donors were 26 × 103/106 and 28 × 103/106 vs 217 × 103/106 and 169 × 103/106, respectively. To account for any influence of T cell proliferation on TREC levels, we assayed T lymphocytes from additional patients with MS and normal individuals for telomere length (n = 20) and telomerase activity (8 MS patients, 16 controls), respectively. There were no significant differences between CD4+ and CD8+ T cells from MS patients and controls. Altogether, our findings suggest that an impaired thymic export function and, as a consequence, altered ability to maintain T cell homeostasis and immune tolerance may play an important pathogenic role in RRMS.

show abstract

“…In both cases, reductions in CD4 and CD8 sjTRECs have been observed after thymectomy. 41,42 However, it remains unclear to what extent complete or partial thymectomy influences homeostatic proliferation by naive CD4 T cells and the diversity of their ab-TCR repertoire. An important limitation of sjTREC assays is that they are a 'bulk' cell population-based assay rather than a single cell assay, and do not allow the simultaneous determination of the function of the cell and its relationship with sjTREC content.…”

Section: Post-thymic Homeostasis Of Human Naive Cd4 T Cellsmentioning

confidence: 99%

Protein tyrosine kinase 7: a novel surface marker for human recent thymic emigrants with potential clinical utility

2011

View full text Add to dashboard Cite

Recent thymic emigrants (RTEs) are antigenically naive T cells that have recently completed intrathymic maturation and have emigrated from the thymus to the periphery. RTEs are clinically and immunologically important as they are essential for maintaining peripheral T cells in sufficient numbers in order to recognize, by their abT-cell receptors (TCRs), a diverse array of foreign peptide antigens. However, RTE frequency and function has been poorly understood because of a lack of surface markers to distinguish them from older non-RTE naive T cells. This review summarizes the biology of the intrathymic generation and function of RTEs, including the recent identification of protein tyrosine kinase 7 (PTK7) as a novel marker for human RTEs of the CD4 (helper) T-cell lineage. PTK7 þ RTEs in adults have a reduced capacity for activationinduced proliferation and cytokine production (interleukin-2 and interferon-g) than older PTK7À naive CD4 T cells. Importantly, this immaturity in CD4 RTE effector function may contribute to the reduced adaptive immune responses observed in situations in which CD4 RTEs predominate, including the fetus, neonate and young infant, and following immune reconstitution, such as post-hematopoietic stem cell transplant. The ability to identify viable CD4 þ RTEs based on PTK7 surface staining may be particularly useful in the infant for better defining the impact of nutritional and environmental factors on thymic output, peripheral T-cell function and adaptive immune responses to vaccination and infection.

show abstract

Effect of Thymectomy on Human Peripheral Blood T Cell Pools in Myasthenia Gravis

Cited by 93 publications

References 31 publications

The Effects of Age, Thymectomy, and HIV Infection on α and β TCR Excision Circles in Naive T Cells

The Effects of Age, Thymectomy, and HIV Infection on α and β TCR Excision Circles in Naive T Cells

Thymic Export Function and T Cell Homeostasis in Patients with Relapsing Remitting Multiple Sclerosis

Protein tyrosine kinase 7: a novel surface marker for human recent thymic emigrants with potential clinical utility

Contact Info

Product

Resources

About