The role of CD80 and CD86 in enhancing CD8(+) cell suppression of HIV replication.
CD8(+) cells activated in the presence of autologous macrophages (Mphi) have an increased ability to suppress HIV replication compared to the same cells stimulated in the absence of Mphi. Blocking the B7 molecules decreases the ability of Mphi to increase CD8(+) cell antiviral activity. In the present study CD8(+) cells exposed to purified forms of both the CD80 and the CD86 molecules during stimulation with anti-CD3 antibodies (Ab) had a greater ability to suppress HIV replication than CD8(+) cells exposed to anti-CD3 Ab alone. The addition of anti-CD86 blocking Ab, but not anti-CD80 blocking Ab, to Mphi decreased their ability to enhance CD8(+) cell suppression of HIV replication. Moreover, anti-CD86 Ab and not anti-CD80 Ab blocked the production of IL-2 by CD8(+) cells stimulated in the presence of Mphi. The incapacity of anti-CD80 Ab to block the enhanced antiviral activity and IL-2 production of CD8(+) cells stimulated in the presence of Mphi 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 Mphi. Thus, while both B7 molecules can deliver a costimulatory signal sufficient to increase CD8(+) cell antiviral activity, CD86 appears to be the molecule that serves as the costimulatory molecule on Mphi to enhance CD8(+) cell suppression of HIV replication. The difference in use of CD86 over CD80 molecules on Mphi by CD8(+) cells mediating the antiviral suppressing activity most likely results from a higher number of Mphi expressing the CD86 molecule compared with the CD80 molecule. This information offers a possible therapeutic approach to increase CD8(+) cell anti-HIV response.
Barker
E
E
Department of Medicine, University of California, San Francisco, California 94143-1270, USA.
Bossart
K N
KN
Fujimura
S H
SH
Levy
J A
JA
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology*; D018122:B7-1 Antigen / Q000276:immunology*; D051940:B7-2 Antigen; D017252:CD3 Complex / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D006678:HIV / Q000502:physiology*; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D046911:Macromolecular Substances; D008264:Macrophages / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000276:immunology*; D014779:Virus Replication
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D017252:CD3 Complex; C497964:CD86 protein, human; D007376:Interleukin-2; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins