Large granular lymphocytes from SCID horses develop potent cytotoxic activity after treatment with human recombinant interleukin 2.

The study explores the ability of large granular lymphocytes (LGL) from horses with severe combined immunodeficiency (SCID) to develop cytotoxic activity when treated with human recombinant interleukin 2 (rIL 2). It found a significant increase in cytotoxic activity under these conditions, indicating that horses with SCID can produce cytotoxic cells similar to natural killer cells.

Objective and Methodology

• The main objective of this study was to investigate the cytotoxicity of Large granular lymphocytes (LGL) from SCID horses once treated with human recombinant interleukin 2 (rIL 2).
• Peripheral blood mononuclear cells from SCID foals were used in the investigation, with an attempt to demonstrate cytotoxic activity.
• The LGL were incubated with 100 U of rIL 2/ml for 24 hours. Post-incubation, 51Cr-release assay was performed to measure cytotoxic activity against YAC-1 lymphoma or K562 erythroleukemia cell lines.

Results and Findings

• Without the rIL 2 incubation, attempts to show cytotoxic activity were unsuccessful.
• With rIL 2 incubation, there was a consistent display of high levels of cytotoxic activity. Specifically, low effector to target ratios (10:1) yielded cytotoxic activity levels of 30 to 50%.
• The monoclonal antibody EqT12 reacted with a large percentage of these cells, and it was found that the level of cytotoxic activity was directly related to the percentage of EqT12+ cells in the preparation.
• In normal horses, the percentage of circulating EqT12+ cells is low (5%) and cytotoxic activity is not usually detectable even with rIL 2 incubation.
• In contrast, the percentage of EqT12+ cells in the blood of SCID horses is high (up to 40%). Likewise, the IL 2-inducible cytotoxic activity is also high in SCID horses.

Conclusions

• These findings indicate that horses with SCID can produce cytotoxic cells with morphologic and functional characteristics similar to natural killer (NK) cells.
• The research contributes to a greater understanding of the immune system’s response and functionality within SCID horses, particularly regarding the role of LGL and rIL 2 in cytotoxic activity.