A comitogenic serum glycoprotein in T lymphocyte activation

Area of Science:

• Immunology
• Molecular Biology

Background:

• Interleukin-2 (IL-2) is vital for helper T-cell function.
• Phytohemagglutinin (PHA) stimulates Interleukin-1 (IL-1) and IL-2 production in human peripheral blood lymphocytes (PBL).

Purpose of the Study:

• To identify factors involved in PHA-induced mitogenesis and IL-2 production in human PBL.
• To characterize a novel serum glycoprotein essential for IL-2 induction.

Main Methods:

• Isolation and characterization of a 90-KD serum glycoprotein from human PBL cultures stimulated with PHA.
• Assessing the biological activity of the purified glycoprotein, including its effect on IL-2 synthesis and T-cell proliferation.
• Investigating the role of sialic acid residues in the glycoprotein's function.

Main Results:

• A 90-KD serum glycoprotein, distinct from other known proteins, is required for PHA-induced PBL mitogenesis.
• The glycoprotein's activity is abolished by removing sialic acid residues.
• This glycoprotein, termed PHILIP (Plasmatic Human Interleukin-2-Inducing Protein), can induce IL-2 production independently of PHA when combined with a soluble mediator from adherent cells.
• The mediator alone, or with serum/PHILIP, induces T-cell mitogenesis but does not support CTL line growth.

Conclusions:

• A novel 90-KD glycoprotein (PHILIP) plays a critical role in the induction of Interleukin-2 synthesis and release.
• PHILIP functions in conjunction with a mediator from adherent cells to promote T-cell mitogenesis.
• This finding provides new insights into the complex regulation of T-cell activation and IL-2 production.