The role of CD80 and CD86 in enhancing CD8(+) cell suppression of HIV replication

CD8(+) cells activated in the presence of autologous macrophages (M phi) ha ve an increased ability to suppress HIV replication compared to the same ce lls stimulated in the absence of M phi. Blocking the B7 molecules decreases the ability of M phi to increase CD8(+) cell antiviral activity. In the pr esent study CD8(+) cells exposed to purified forms of both the CD80 and the CD86 molecules during stimulation with anti-CDS antibodies (Ab) had a grea ter ability to suppress HIV replication than CD8(+) cells exposed to anti-C DS Ab alone. The addition of anti-CD86 blocking Ab, but not anti-CD80 block ing Ab, to M phi decreased their ability to enhance CD8(+) cell suppression of HIV replication. Moreover, anti-CD86 Ab and not anti-CD80 Ab blocked th e production of IL-2 by CD8(+) cells stimulated in the presence of M phi. T he incapacity of anti-CD80 Ab to block the enhanced antiviral activity and IL-2 production of CD8(+) cells stimulated in the presence of M phi was not due to the inability of this Ab to function since anti-CD80 Ab are able to block proliferation of CD8(+) cells cultured in the presence of M phi. Thu s, while both B7 molecules can deliver a costimulatory signal sufficient to increase CD8(+) cell antiviral activity, CD86 appears to be the molecule t hat serves as the costimulatory molecule on M phi to enhance CD8(+) cell su ppression of HIV replication. The difference in use of CD86 over CD80 molec ules on M phi by CD8(+) cells mediating the antiviral suppressing activity most likely results from a higher number of M phi expressing the CD86 molec ule compared with the CD80 molecule. This information offers a possible the rapeutic approach to increase CD8(+) cell anti-HIV response. (C) 1999 Acade mic Press.