CD4 T Cells Treated with gp120 Acquire a CD45R0+/CD45RA+ Phenotype

Area of Science:

• Immunology
• Virology
• Cell Biology

Background:

• HIV infection causes defects in CD4 T cells, including an increase in CD4+CD45R0+/CD45RA+ T cells.
• The origin and mechanism behind this increase in CD4 T cell subsets during HIV infection remain poorly understood.

Purpose of the Study:

• To investigate the mechanism by which HIV gp120 affects CD4 T cell populations.
• To determine the role of gp120-CD4 interactions in the generation and apoptosis of specific CD4 T cell subsets.

Main Methods:

• Treatment of activated primary human CD4 T cells with HIV gp120.
• Analysis of CD4 T cell phenotypes using CD45R0 and CD45RA markers.
• Assessment of apoptosis in different CD4 T cell subsets.
• Inhibition of gp120-CD4 interaction using sCD4 and Lck activity inhibition.

Main Results:

• gp120 treatment decreased effector memory (CD45R0+/CD45RA-) CD4 T cells while increasing mixed phenotype (CD45R0+/CD45RA+) cells.
• The CD45R0+/CD45RA+ CD4 T cells preferentially underwent apoptosis compared to other subsets.
• Blocking gp120-CD4 interaction or Lck activity reversed the increase in CD45R0+/CD45RA+ cells and reduced their apoptosis.

Conclusions:

• gp120 ligation of the CD4 receptor drives an increase in the CD45R0+/CD45RA+ CD4 T cell subset.
• This gp120-induced increase in CD45R0+/CD45RA+ CD4 T cells leads to their subsequent apoptosis in a CD4-dependent manner.
• These findings elucidate a mechanism contributing to CD4 T cell depletion in HIV infection.