Cyclosporine does not prevent cytoplasmic calcium changes associated with lymphocyte activation

Area of Science:

• Immunology
• Cell Biology
• Biochemistry

Background:

• Fluorescent reagents enable quantification of cytoplasmic calcium in lymphocytes.
• Lymphocyte stimulation leads to a rapid, significant increase in cytoplasmic calcium.
• This calcium increase is hypothesized to be crucial for mitogenic commitment.

Purpose of the Study:

• To investigate the requirement of calcium influx for T cell mitogenic commitment.
• To determine the role of extracellular calcium concentration in T cell activation.
• To examine the effect of cyclosporine on early cytoplasmic calcium changes in activated T cells.

Main Methods:

• Utilizing fluorescent calcium indicators to monitor intracellular calcium levels in lymphocytes.
• Exposing T cells to concanavalin A (Con A) under varying extracellular calcium concentrations.
• Assessing T cell division and mitogenesis.
• Investigating the impact of cyclosporine (Cys) on calcium dynamics during T cell activation.

Main Results:

• T cell division requires extracellular calcium; no mitogenesis occurs below 10(-5)M calcium.
• Concanavalin A stimulation leads to a rapid, >2-fold increase in cytoplasmic calcium.
• Cyclosporine does not inhibit the early changes in cytoplasmic calcium levels of activated T cells.

Conclusions:

• Extracellular calcium influx is an absolute requirement for T cell mitogenic commitment.
• The plasma membrane plays a key role in regulating cytoplasmic calcium changes during lymphocyte activation.
• Cyclosporine does not appear to inhibit T cell activation by altering early calcium signaling.