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 cel ls by releasing cytotoxic granules, The primary objective of this stud y was to determine whether the activity of granzyme A, a serine protea se in the killing granules of CTLs is altered in HIV-infected hemophil iacs. A sensitive colorimetric assay that measures cleavage of a synth etic substrate, N-alpha-benzyloxycarbonyl-l-lysine thiobenzyl ester (B LT), 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 H IV-seropositive hemophiliacs was significantly lower than granzyme A a ctivity in cells from HIV-seronegative hemophiliacs (0.48 units +/- 0. 086/CD8(+) T cell and 1.573 +/- 0.434 units/CD8(+) T cell, respectivel y; p < 0.005). These results indicate that cytotoxic cells in HIV-infe cted hemophiliacs have reduced granzyme A activity, which may result i n a defect in CTL-mediated cell killing in these patients.