alexa Longitudinal assessment of de novo T cell production in relation to HIV-associated T cell homeostasis failure.


Journal of Clinical & Cellular Immunology

Author(s): Chattopadhyay PK, Douek DC, Gange SJ, Chadwick KR, Hellerstein M,

Abstract Share this page

Abstract Loss of circulating CD4+ T cells in HIV-1 disease is balanced by CD8+ lymphocytosis to maintain normal CD3+ T cell counts [blind T cell homeostasis (TCH)]. However, for unknown reasons TCH generally fails 1.5-2.5 years before clinically defined AIDS. We investigated whether TCH failure was associated with changes in thymic production of T cells. Using specimens stored prospectively in the Multicenter AIDS Cohort Study (MACS), we measured expression of signal-joint T cell receptor excision circles (sjTRECs), a marker for thymic T cell production, and the fraction of proliferating naive and memory T cells during a 6-8 year period bracketing TCH failure. Segmented regression modeling assessed (1) rates of change in TREC levels before and after TCH failure, and (2) whether these were affected by cellular proliferation, which may dilute sjTREC levels. TCH failure was associated with a large decline in sjTREC (median 1109-fold, p = 0.028); the rate of this decline was only slightly affected when increased proliferation of naive T cells or other peripheral lymphocytes was taken into account. Preferential loss of naive CD4+ T cells was also noted before TCH failure, as has been seen in other studies. These results suggest that deficits in de novo T cell production, either through the decline of thymic function or the destruction of naive T cells, are likely to play an important role in TCH failure and progression of HIV-1 disease.
This article was published in AIDS Res Hum Retroviruses and referenced in Journal of Clinical & Cellular Immunology

Relevant Expert PPTs

Relevant Speaker PPTs

Recommended Conferences

Relevant Topics

Peer Reviewed Journals
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version