Central memory CD8+ T cells appear to have a shorter lifespan and reduced abundance as a function of HIV disease progression.
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 ((2)H(2)O), (2)H-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 (T(CM)) cells expressing IL-7Ralpha and CD8(+)CD45RA(+)CCR7(-)CD28(-) RA effector memory (T(EMRA)) cells expressing CD57. In pilot studies in HIV-infected subjects, T(CM) cells appeared to have a shorter half-life and reduced abundance, particularly in those with high viral loads; T(EMRA) 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-7Ralpha(+) T(CM) 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.
Division of Experimental Medicine and Department of Medicine, University of California, San Francisco, CA 94110, USA.
Kristin
K
Ladell
Marc K
MK
Hellerstein
Denise
D
Cesar
Robert
R
Busch
Drina
D
Boban
Joseph M
JM
McCune
D000328:Adult; D018959:CD57 Antigens / Q000096:biosynthesis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle / Q000276:immunology; D002470:Cell Survival / Q000276:immunology*; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000276:immunology* / Q000473:pathology*; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D053727:Interleukin-18 Receptor alpha Subunit / Q000096:biosynthesis; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D020395:Receptors, Interleukin-7 / Q000096:biosynthesis; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*
D018959:CD57 Antigens; C508572:IL18R1 protein, human; D053727:Interleukin-18 Receptor alpha Subunit; D020395:Receptors, Interleukin-7; C415350:interleukin-7 receptor, alpha chain