Expression and function of B7-1 (CD80) and B7-2 (CD86) on human epidermal Langerhans cells

Area of Science:

• Immunology
• Cell Biology
• Dermatology

Background:

• T cell activation requires both T cell receptor (TCR) triggering and costimulatory signals, primarily mediated by CD28.
• Langerhans cells (LC) are crucial antigen-presenting cells in the epidermis, playing a role in initiating immune responses.
• CD28 interacts with its ligands, B7-1 (CD80) and B7-2 (CD86), to provide essential costimulatory signals for T cell activation.

Purpose of the Study:

• To investigate the expression and functional role of B7-1 and B7-2 ligands on human Langerhans cells.
• To determine the relative contribution of B7-1 and B7-2 to T cell costimulation by Langerhans cells.
• To elucidate the role of these ligands in T cell proliferation and immune responses initiated by epidermal antigen-presenting cells.

Main Methods:

• Analysis of B7-1 and B7-2 expression on freshly isolated and cultured human Langerhans cells (LC).
• Use of monoclonal antibodies (mAB) against B7-1 and B7-2, and CTLA4-Ig fusion protein to block ligand-receptor interactions.
• Assessment of T cell proliferation in mixed epidermal cell-lymphocyte reactions (mELR) using allogeneic and recall antigens.

Main Results:

• Freshly isolated LC (fLC) express significant B7-2, with increased expression upon in vitro culture.
• B7-1 is initially undetectable on fLC but appears after 3 days of in vitro culture.
• Anti-B7-2 mAB and CTLA4-Ig significantly inhibited T cell proliferation, while anti-B7-1 mAB had minimal effect, indicating B7-2 is the dominant ligand.

Conclusions:

• B7-2 is the predominant ligand for CD28/CTLA4 on human Langerhans cells.
• B7-2 plays a critical role in the costimulatory function of human LC, supporting T cell proliferation.
• The function of human LC in T cell costimulation is largely independent of B7-1 expression.