[HTML][HTML] Subpopulations of long-lived and short-lived T cells in advanced HIV-1 infection

MK Hellerstein, RA Hoh, MB Hanley… - The Journal of …, 2003 - Am Soc Clin Investig
MK Hellerstein, RA Hoh, MB Hanley, D Cesar, D Lee, RA Neese, JM McCune
The Journal of clinical investigation, 2003Am Soc Clin Investig
Antigenic stimulation of T cells gives rise to short-lived effector cells and long-lived memory
cells. We used two stable isotope-labeling techniques to identify kinetically distinct
subpopulations of T cells and to determine the effect of advanced infection with HIV-1. Long-
term deuterated water (2H2O) incorporation into DNA demonstrated biphasic accrual of total
and of memory/effector (m/e)–phenotype but not naive-phenotype T cells, consistent with the
presence of short-lived and longer-lived subpopulations within the m/e-phenotype T cell …
Antigenic stimulation of T cells gives rise to short-lived effector cells and long-lived memory cells. We used two stable isotope-labeling techniques to identify kinetically distinct subpopulations of T cells and to determine the effect of advanced infection with HIV-1. Long-term deuterated water (2H2O) incorporation into DNA demonstrated biphasic accrual of total and of memory/effector (m/e)–phenotype but not naive-phenotype T cells, consistent with the presence of short-lived and longer-lived subpopulations within the m/e-phenotype T cell pool. These results were mirrored by biphasic die-away kinetics in m/e- but not naive-phenotype T cells after short-term 2H-glucose labeling. Persistent label retention was observed in a subset of m/e-phenotype T cells (presumably memory T cells), confirming the presence of T cells with very different life spans in humans. In advanced HIV-1 infection, much higher proportions of T cells were short-lived, compared to healthy controls. Effective long-term anti-retroviral therapy restored values to normal. These results provide the first quantitative evidence that long-lived and quiescent T cells do indeed predominate in the T cell pool in humans and determine T cell pool size, as in rodents. The greatest impact of advanced HIV-1 infection is to reduce the generation of long-lived, potential progenitor T cells.
The Journal of Clinical Investigation