Activity of granzyme A, a serine protease in the killing granules of cytotoxic T lymphocytes, is reduced in cells from HIV-infected hemophiliacs

Cytotoxic CD8(+) T lymphocytes (CTLs) kill virally infected target cells by releasing cytotoxic granules, The primary objective of this study was to determine whether the activity of granzyme A, a serine protease in the killing granules of CTLs is altered in HIV-infected hemophiliacs. A sensitive colorimetric assay that measures cleavage of a synthetic substrate, N-alpha-benzyloxycarbonyl-l-lysine thiobenzyl ester (BLT), was used to quantitate granzyme A activity, Granzyme A activities from hemophiliacs were normalized to granzyme A activities of healthy donors run concurrently, Granzyme A activity in CD8(+) T cells from HIV-seropositive hemophiliacs was significantly lower than granzyme A activity in cells from HIV-seronegative hemophiliacs (0.48 units +/- 0.086/CD8(+) T cell and 1.573 +/- 0.434 units/CD8(+) T cell, respectively; p < 0.005). These results indicate that cytotoxic cells in HIV-infected hemophiliacs have reduced granzyme A activity, which may result in a defect in CTL-mediated cell killing in these patients.