Central Memory CD8+ T Cells Appear to Have a Shorter Lifespan and Reduced Abundance as a Function of HIV Disease Progression

Abstract

Progressive HIV disease has been associated with loss of memory T cell responses to Ag. To better characterize and quantify long-lived memory T cells in vivo, we have refined an in vivo labeling technique to study the kinetics of phenotypically distinct, low-frequency CD8+ T cell subpopulations in humans. HIV-negative subjects and antiretroviral-untreated HIV-infected subjects in varying stages of HIV disease were studied. After labeling the DNA of dividing cells with deuterated water (2H2O), 2H-label incorporation and die-away kinetics were quantified using a highly sensitive FACS/mass spectrometric method. Two different populations of long-lived memory CD8+ T cells were identified in HIV-negative subjects: CD8+CD45RA−CCR7+CD28+ central memory (TCM) cells expressing IL-7Rα and CD8+CD45RA+CCR7−CD28− RA effector memory (TEMRA) cells expressing CD57. In pilot studies in HIV-infected subjects, TCM cells appeared to have a shorter half-life and reduced abundance, particularly in those with high viral loads; TEMRA cells, by contrast, retained a long half-life and accumulated in the face of progressive HIV disease. These data are consistent with the hypothesis that IL-7Rα+ TCM cells represent true memory CD8+ T cells, the loss of which may be responsible in part for the progressive loss of T cell memory function during progressive HIV infection.

Stable Phenotypic Changes of the Host T Cells Are Essential to the Long-Term Stability of Latent HIV-1 Infection

“…ϩ T CM cells in HIV-1 patients, a recent study suggested that the CD8 ϩ T CM half-life seems reduced from a 1/2 of ϳ100 days to a 1/2 of ϳ50 days (8). Even if we used a 1/2 of ϳ50 days for latently HIV-1 infected CD4…”

CD4 T Cell Depletion at the Cervix during HIV Infection Is Associated with Accumulation of Terminally Differentiated T Cells

“…Previous studies have demonstrated that the differentiation status of T cells is associated with the rate of HIV disease progression (4,20,34,40,47). Burgers et al (4) showed that higher frequencies of early CD8 memory cells during early HIV infection were associated with subsequently lower viral set points.…”

“…Further, individuals who are able to better control HIV infection have a preserved CM pool, (40,47), while individuals with a reduced CM CD4 pool had increased plasma HIV load (20).…”

In vivo kinetics and nonradioactive imaging of rapidly proliferating cells in graft-versus-host disease

“…Additionally, we measured these processes in multiple anatomic compartments. Previous studies employed mathematical modeling to hypothesize in vivo cell kinetics outside of the circulation while measuring deuterium label gain and loss in circulating cells (18,19,21,22,24,27,30,(50)(51)(52)(53)(54). In contrast, we obtained quantitative measurements of deuterium gain and loss in T cell subsets from lymphoid and target organs, and we found the same subset (i.e., Treg) to behave differently in the spleen compared with the liver.…”