Reevaluation of T cell receptor excision circles as a measure of human recent thymic emigrants.

نویسندگان

  • Ping Ye
  • Denise E Kirschner
چکیده

The human thymus exports newly generated T cells to the periphery. As no markers have been identified for these recent thymic emigrants (RTE), it is presently impossible to measure human thymic output. T cell receptor excision circles (TREC) have been recently used to assess thymic output during both health and disease. Using a mathematical model, we quantify age-dependent changes both in the number of RTE generated per day and in TREC concentration during an 80-year lifespan. Through analyses, we demonstrate that RTE and peripheral T cell division have the same potential to affect TREC concentration at any age in healthy people. T cell death also influences TREC concentration, but to a lesser extent. During aging, our results indicate that thymic involution primarily induces an age-dependent decline in TREC concentrations within both CD4(+) and CD8(+) T cell populations. We further apply this model for studying TREC concentration during HIV-1 infection. Our analyses reveal that a decrease in thymic output is the major contributor to the decline in TREC concentration within CD4(+) T cells, whereas both increased peripheral T cell division and decreased thymic output induce the decline in TREC concentration within CD8(+) T cells. Therefore, we suggest that T cell turnover should be examined together with TREC concentration as a measure of RTE. If peripheral T cell division remains relatively unchanged, then TREC concentration indeed reflects thymic output.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Measuring emigration of human thymocytes by T-cell receptor excision circles.

Recent advances in characterizing thymic function confirm the importance of thymus to T-cell diversity in the periphery of both children and adults during both health and disease. Lack of a marker to identify human recent thymic emigrants (RTEs) is the biggest hurdle to accurately characterizing and quantifying thymic output. T-cell receptor excision circles (TRECs) are used as an assay to meas...

متن کامل

Recent Thymic Emigrants Do Not Account for the Increased Number of T- Cells Seen in the Lungs of Stable Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) patients have an increased number of T cells within their lungs. It is unknown whether these T cells, remain there forever or if there is a continuous turnover from the blood. In the adult, there is a significant T lymphocytopoiesis from the thymus producing cells known as recent thymic emigrants (RTEs). T cell receptor excision circles (TREC) are a ...

متن کامل

Human CD4+ T cell recent thymic emigrants are identified by protein tyrosine kinase 7 and have reduced immune function

CD4(+) recent thymic emigrants (RTEs) comprise a clinically and immunologically important T cell population that indicates thymic output and that is essential for maintaining a diverse alphabeta-T cell receptor (TCR) repertoire of the naive CD4(+) T cell compartment. However, their frequency and function are poorly understood because no known surface markers distinguish them from older non-RTE ...

متن کامل

T cell receptor gene deletion circles identify recent thymic emigrants in the peripheral T cell pool.

Progenitor cells undergo T cell receptor (TCR) gene rearrangements during their intrathymic differentiation to become T cells. Rearrangements of the variable (V), diversity (D), and joining (J) segments of the TCR genes result in deletion of the intervening chromosomal DNA and the formation of circular episomes as a byproduct. Detection of these extrachromosomal excision circles in T cells loca...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:
  • Journal of immunology

دوره 168 10  شماره 

صفحات  -

تاریخ انتشار 2002