Biological properties of suppressive E-receptor factor on lymphokine function.

Area of Science:

• Immunology
• Cell Biology

Background:

• A novel immunosuppressive factor, suppressive E-receptor (SER) factor, was isolated from malignant ascites fluids.
• SER exhibits serological cross-reactivity with the E-receptor of human peripheral blood T lymphocytes.

Purpose of the Study:

• To investigate the effect of SER on lymphokine functions during polyclonal T cell activation.
• To elucidate the mechanism of SER's anti-proliferative action on human mononuclear cells.

Main Methods:

• Assessing SER's impact on phytohemagglutinin (PHA) and anti-T3 antibody-induced T cell activation in vitro.
• Analyzing cell cycle progression, DNA synthesis, and interleukin-2 (IL-2) receptor expression in SER-treated cells.
• Evaluating the effect of exogenous IL-2 and IL-1 on SER-mediated inhibition.

Main Results:

• SER demonstrated potent immunosuppressive activity at nanomolar concentrations, most effective when added early during T cell stimulation.
• SER induced cell cycle arrest at the G1 phase, leading to growth arrest and eventual cell death, particularly in normal lymphoid cells.
• SER interfered with IL-2-driven proliferation of human mononuclear cells and a murine cytotoxic T cell line, though high doses of IL-2 could partially overcome this effect.
• SER minimally inhibited early IL-2 receptor expression but did not block its full expression by 48 hours, suggesting it affects later events in T cell activation.

Conclusions:

• SER functions as a noncytolytic anti-proliferative factor impacting T cell-mediated immune responses.
• The mechanism of SER involves interference with a late stage of T cell activation, potentially within the DNA replication pathway.
• SER's effects on IL-2 receptor expression indicate a specific modulation rather than a complete blockade of T cell activation signaling.