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

Pratip K. Chattopadhyay, Daniel C. Douek, Stephen J. Gange, Karen R. Chadwick, Marc Hellerstein, Joseph B. Margolick

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)501-507
Number of pages7
JournalAIDS research and human retroviruses
Volume22
Issue number6
DOIs
StatePublished - Jun 2006

ASJC Scopus subject areas

  • Immunology
  • Virology
  • Infectious Diseases

Fingerprint

Dive into the research topics of 'Longitudinal assessment of de novo T cell production in relation to HIV-associated T cell homeostasis failure'. Together they form a unique fingerprint.

Cite this