Teleost B7 expressed on monocytes regulates T cell responses

Area of Science:

• Immunology
• Evolutionary Biology
• Comparative Vertebrate Studies

Background:

• Professional antigen-presenting cells (APCs) activate T cells in mammals, crucial for adaptive immunity.
• B7 family molecules on APCs are key for T cell stimulation, but their presence in nonmammalian vertebrates is unconfirmed.

Purpose of the Study:

• To investigate the evolutionary origins of APCs.
• To identify and characterize B7 family molecules in teleost fish (Takifugu rubripes).

Main Methods:

• Identification of three B7 family members (B7-H1/DC, B7-H3, B7-H4) in fugu.
• Analysis of B7 expression on fugu blood monocytes and their interaction with T cells.
• Assessment of fugu B7 molecule effects on T cell proliferation and cytokine production (IL-10, IFN-gamma, IL-2).

Main Results:

• Fugu B7-H1/DC, B7-H3, and B7-H4 were expressed on blood monocytes, which also expressed MHC class II.
• Fugu B7 molecules bound to activated T cells, indicating T cell receptor expression.
• B7-H1/DC inhibited T cell proliferation while upregulating IL-10 and IFN-gamma; B7-H3 and B7-H4 promoted proliferation via IL-2 induction and IL-10 suppression.

Conclusions:

• Fugu B7-expressing monocytes function as APCs, regulating T cell responses.
• A costimulatory system involving B7 molecules and T cell receptors has evolved in fish.
• These findings suggest an ancient evolutionary origin for APCs and immune costimulation predating mammals.