De. Lewis et al., HIV-specific cytotoxic T lymphocyte precursors exist in a CD28-CD8+T cell subset and increase with loss of CD4 T cells, AIDS, 13(9), 1999, pp. 1029-1033
Objectives: To determine whether the CD28-CD8+ T cells that develop during
HIV infection contain HIV-specific cytotoxic precursor cells.
Design: CD8 subpopulations from six asymptomatic HIV-positive adults, with
varying degrees of CD4 T cell loss, were sorted by flaw cytometry and HIV-s
pecific precursor cytotoxic T lymphocyte frequencies were measured. Three p
opulations of CD8 T cells were tested: CD28+CD57- T cells, CD28-CD57+ T cel
ls (thought to be memory cells) and CD28-CD57- T cells (function unknown).
Methods: Sorted CD8 subsets were stimulated with antigen presenting cells e
xpressing HIV-1 Gag/Pol molecules. Cytotoxic T cell assays on Gag/Pol expre
ssing Cr-51-labeled Epstein-Barr virus transformed autologous B cells lines
or control targets were performed after 2 weeks. Specific lysis and precur
sor frequencies were calculated.
Results: Both CD28 positive and CD28-CD57+ populations contained appreciabl
e numbers of precursors (9-1720 per 10(6) CD8+ T cells). However, the CD28-
CD57-population had fewer precursors in five out of six people studied. Mor
e CD28 positive HIV-specific cytotoxic T lymphocyte precursors were found i
n patients with CD4:CD8 ratios > 1, whereas more CD28-CD57+ precursors were
found in patients whose CD 1 : CD8 ratios were < 1 (r(2), 0.68).
Conclusions: Memory HIV-specific precursor cytotoxic T lymphocytes are foun
d in both CD28 positive and CD28-CD8+ cells, however, a CD28-CD57-subpopula
tion had fewer. Because CD28-CD57+ cells are antigen-driven with limited di
versity, the loss of CD28 on CD8 T cells during disease progression may red
uce the response to new HIV mutations; this requires further testing. (C) 1
999 Lippincott Williams & Wilkins.