CD28 costimulation increases CD8+ cell suppression of HIV replication

Area of Science:

• Immunology
• Virology
• Cell Biology

Background:

• CD8+ T cells play a role in non-cytotoxic suppression of HIV replication.
• CD28, a membrane receptor on CD8+ T cells, interacts with B7 antigens on antigen-presenting cells (APCs).

Purpose of the Study:

• To investigate the role of CD28 costimulation in enhancing CD8+ T cell-mediated suppression of HIV replication.
• To determine the potential clinical utility of CD28 triggering in HIV-infected individuals, including those with AIDS.

Main Methods:

• Utilized anti-CD28 antibodies to stimulate CD8+ T cells and assess HIV replication.
• Employed CTLA4Ig fusion protein to block CD28-B7 interactions and observed the effects on antiviral activity.
• Measured IL-2 production and IL-2 receptor (IL-2R) expression by CD8+ T cells following CD28 costimulation.
• Used anti-IL-2 and anti-IL-2R antibodies to investigate the role of the IL-2 pathway.

Main Results:

• Optimal inhibition of HIV production by CD8+ T cells was achieved by triggering CD28 with anti-CD28 antibodies.
• Blocking CD28-B7 interaction with CTLA4Ig reduced the enhancement of CD8+ T cell antiviral activity by macrophages, but this could be reversed by anti-CD28 Ab.
• CD28 costimulation led to increased IL-2 production and IL-2R expression by CD8+ T cells, correlating with enhanced antiviral activity.
• Engagement of CD28 restored the HIV-suppressive ability of CD8+ T cells from individuals with AIDS.

Conclusions:

• Triggering CD28 on CD8+ T cells enhances their capacity to suppress HIV replication.
• The IL-2 pathway is involved in the CD28-mediated antiviral effect.
• CD28 stimulation holds promise as a therapeutic strategy for HIV-infected symptomatic patients, including those with AIDS.