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

AIDS Res Hum Retroviruses. 1996 Feb 10;12(3):235-9. doi: 10.1089/aid.1996.12.235.


Cytotoxic CD8+ 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 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cohort Studies
  • Female
  • Granzymes
  • HIV Seronegativity
  • HIV Seropositivity / blood
  • HIV Seropositivity / complications*
  • HIV Seropositivity / enzymology
  • Hemophilia A / blood
  • Hemophilia A / complications
  • Hemophilia A / enzymology*
  • Hemophilia B / blood
  • Hemophilia B / complications
  • Hemophilia B / enzymology*
  • Humans
  • Lysine / analogs & derivatives
  • Lysine / metabolism
  • Male
  • Serine Endopeptidases / metabolism*
  • T-Lymphocytes, Cytotoxic / enzymology*


  • thiobenzyl benzyloxycarbonyl-L-lysinate
  • Granzymes
  • Serine Endopeptidases
  • GZMA protein, human
  • Lysine