The relative resistance of HIV type 1-infected chimpanzees to AIDS correlates with the maintenance of follicular architecture and the absence of infiltration by CD8(+) cytotoxic T lymphocytes

Lymphoid tissues are the focus of critical events in HIV pathogenesis, Pers istent and high levels of virus production, extensive trapping of virus par ticles in germinal centers, and progressive degenerative changes in lymph n ode architecture are characteristics of progressive HIV-1 infection. Infilt rates of granzyme B- and TIA-expressing CD8(+) "cytotoxic" T lymphocytes (C TLs) precede involution of germinal centers in humans who develop AIDS. Sim ilar to humans, HIV-P infection in chimpanzees is active and persistent, Ho wever, in contrast to humans, they remain relatively resistant to AIDS. Lym ph node biopsies from chimpanzees infected with HIV-1 or a related chimpanz ee lentivirus were studied for the level and pattern of virus expression, c hanges in lymphoid architecture, CD8+ T cell infiltrates and the presence o r absence of CTL markers. In stark contrast to HIV-l-infected humans, lymph nodes from infected chimpanzees had little virus deposition in germinal ce nters and a paucity of virus-expressing cells. Although some of the lymph n odes examined from infected animals had moderate follicular hyperplasia wit h infiltrating CD8(+) T cells, none had evidence of follicular fragmentatio n. Most importantly, in marked contrast to infected humans, CD8(+) T cells infiltrating the germinal center were negative for the CTL marker granzyme B. This evidence suggests that the infiltration of CD8(+) CTLs into the ger minal centers of lymph nodes may be a key determinant in AIDS pathogenesis.