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The Use of Kernel Estimators in Describing Human T Lymphocyte Proliferation Induced by Phorbol Esters and Ca²⁺ Ionophore

Department of Biostatistics Medical College of Virginia P.O. Box 32 Virginia Commonwealth University Richmond, VA 23298

Carl W. McCrady

Department of Biostatistics Medical College of Virginia P.O. Box 32 Virginia Commonwealth University Richmond, VA 23298

A nonparametric method for analyzing the mitogenic count data generated from in vitro T cell stimulation by phorbol dibutyrate (PDBu) and ionomycin (I) is described. Antigen receptor initiated T cell activation is transduced by the combined second messenger actions of phospholipid metabolites diacylglycerol (DAG) and inositol triphosphate (IP₃). DAG activates protein kinase C, and IP₃ serves to elevate cytosolic Ca²⁺ levels. Pharmacological agents, such as phorbol esters and the Ca²⁺ ionophore ionomycin, mimic DAG and IP₃, respectively. Consequently, they can be used to initiate T lymphocyte activation and subsequent proliferation. Given mitogenic count data measured by ³H-thymidine incorporation, a kernel estimate of the proliferative response surface is used to develop a confidence region for the optimal combination level of PDBu and ionomycin for maximum T cell proliferation. The experimental data analysis was validated with a small computer simulation study. The resulting confidence regions have high coverage probabilites robust with respect to the shape of the underlying proliferative response surface. This bias robustness is important in this application because the shape of the response surface may vary among individuals. Thus, this procedure will allow for optimization of an individual's T cell proliferative response.

International Journal of Toxicology, Vol. 7, No. 7, 939-951 (1988)
DOI: 10.3109/10915818809014525


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