A Study of the Functional Potential of Mouse T-Cell Clones

Abstract

The development of techniques for the cloning of single antigen-responsive T cells, and their subsequent expansion to provided large numbers of relatively homogeneous cells, has provided a powerful tool for analysing the biology and bio-chemistry of T-lymphocyte function. Cloned T-cell lines have played a central role in the acquisition of knowledge of the T-cell antigen receptor and have provided new insights into the recognitive and functional diversity of different T-cell subsets. In the latter area, two general approaches have been utilized. In the first, T cells obtained directly from animals, or following various in vitro manipulations, have been cloned in microplate wells in the presence of appropriate antigen and growth factors, and the activity of the developing clones has been assayed in situ. With the recent development of high efficiency cloning systems (Chen et al. 1982; Moretta et al. 1983; Pfizenmaier et al. 1984), such limiting dilution analysis is potentially an extremely powerful method for dissecting immune responses. However, there are also several problems: the small size of the primary clones severely restricts the number of parameters that can be analyzed; the readout is measured in an all-or-none manner rather than quantitatively, and the frequency of responding cells is often meaningless, as the cloning efficiency, the sensitivity of the detection system, and the antigen specificities of the clones are largely unknown. In the second approach, established T-cell lines are studied in a variety of functional assays, but here there are major problems as to whether a given T-cell clone can be considered “typical” and whether the function of an aged cell line reliably reflects the functional potential of the progenitor cell.

This work was supported by grant AI-15384 from the National Institutes of Health