EXPRESSION OF GRANZYME-B BY CYTOTOXIC T-LYMPHOCYTES IN THE LYMPH-NODES OF HIV-INFECTED PATIENTS

During HIV infection the architecture of secondary lymphoid tissues is severely disrupted, In particular the germinal centers, which play a key role in the orchestration of the secondary immune response, underg o gross phenotypic alterations, leading to a complete destruction of t he germinal center microenviromnent, The precise mechanisms responsibl e for the lymphoid tissue destruction in HIV infection are still unkno wn, However, the large influx of CD8(+) T lymphocytes suggests an impo rtant role for T cell-mediated cytotoxicity, To establish whether the infiltrating CD8(+) T lymphocytes are killing competent, we investigat ed the expression of granzyme B, which is known to be present in the c ytotoxic granules of NK cells and ''activated') CTLs with cytolytic po tential, We observed a 20-fold increase in the percentage of granzyme B-expressing CD8(+) T cells in both the germinal center and the interf ollicular areas in HIV patients relative to HIV-negative controls, Thi s increase was present in patients with early-stage disease (i.e., abs olute CD4(+) T cell count > 500 mu l) as well as in patients with inte rmediate and late-stage disease, Thus, from relatively early stages of HIV infection onward large numbers of killing competent T lymphocytes are present in the lymphoid tissues, a finding that supports the noti on that CTL act as mediators of destruction of immune function during HIV infection.