CD28 costimulation increases CD8+ cell suppression of HIV replication.
A subset of CD8+ T lymphocytes that expresses CD28, a membrane receptor for B7 differentiation Ags found on APCs, is primarily responsible for the noncytotoxic suppression of HIV replication in CD4+ cells of HIV-infected individuals. Optimal inhibition of HIV production by CD8+ cells occurs after triggering the CD28 molecule on the cells with anti-CD28 Abs during stimulation. Blocking the interaction of the CD28 and B7 molecules with a CTLA4Ig fusion protein abrogates the ability of autologous macrophages to enhance this CD8+ cell antiviral activity. This blocking effect can be reversed by treating the CD8+ cells with anti-CD28 Ab. The increase in antiviral activity following CD28 costimulation correlates with enhanced IL-2 production and IL-2R expression by CD8+ cells. Prevention of IL-2 binding to its receptor, using anti-IL-2 or anti-IL-2R Abs, reduces the ability of CD8+ cells to suppress HIV replication following CD28 costimulation. Importantly, engagement of the CD28 molecule during stimulation of CD8+ cells from individuals with AIDS restored the ability of their cells to suppress HIV replication. Thus, triggering the CD28 molecule during stimulation of CD8+ cells could clinically benefit HIV-infected symptomatic patients.
Barker
E
E
Department of Medicine, University of California School of Medicine, San Francisco 94143, USA.
Bossart
K N
KN
Fujimura
S H
SH
Levy
J A
JA
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology; D000276:Adjuvants, Immunologic / Q000502:physiology; D019138:Antibodies, Blocking / Q000494:pharmacology; D000938:Antigen-Presenting Cells / Q000378:metabolism; D000998:Antiviral Agents / Q000276:immunology; D018122:B7-1 Antigen / Q000096:biosynthesis; D001665:Binding Sites / Q000276:immunology; D018106:CD28 Antigens / Q000096:biosynthesis / Q000502:physiology*; D016827:CD8 Antigens / Q000502:physiology*; D006678:HIV / Q000276:immunology* / Q000502:physiology; D006801:Humans; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000276:immunology; D008213:Lymphocyte Activation; D015375:Receptors, Interleukin-2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D014779:Virus Replication / Q000276:immunology*
D000276:Adjuvants, Immunologic; D019138:Antibodies, Blocking; D000998:Antiviral Agents; D018122:B7-1 Antigen; D018106:CD28 Antigens; D016827:CD8 Antigens; D007376:Interleukin-2; D015375:Receptors, Interleukin-2