Journal oflmmunological Methods, 50 (1982) R51--R63 R51 Elsevier Biomedical Press Review article CONTROL OF LYMPHOCYTE STIMULATION IN VITRO: 'HELP' AND 'SUPPRESSION' IN THE LIGHT OF LYMPHOID POPULATION DYNAMICS STELLA C. KNIGHT Division of Rheumatology, Clinical Research Centre, Watford Road, Harrow, Middlesex, U.K. (Received 27 October 1981, accepted 27 November 1981) Markers on the surfaces of lymphocytes are used increasingly to identify subpopula- tions. The functions of these subsets of cells are often inferred from their effects on stimu- lation of lymphocytes in vitro. For example, T cells expressing the antigen OKT4 have been described as 'helper cells' and those with OKT8 as 'suppressor cells' (Reinhertz and Schlossman, 1980). However, correlations reported between the surface markers and function are not found consistently (Goodwin and Williams, 1979; Moretta, 1981). Study of population dynamics of lymphocyte growth in culture can provide an explanation for variable results and aid the definition of functions of lymphocytes with different markers. Thus, although proliferation of lymphocytes stimulated with mitogen may be reduced on addition of putative 'suppressor cells', there are many ways in which this suppressive effect may occur without postulating the presence of cells with innate suppressor func- tion. An optimal response to mitogen with the new combination of cells may require an increased or decreased total number of cells in culture, a higher or lower dose of stimu- lant or a longer or shorter culture period. An inhibition of lymphocyte proliferation may also occur in any stimulated culture at high cell densities and this parallels 'contact inhibi- tion' of the growth of cell lines. Regulation of growth in lymphocyte clones may, there- fore, be mediated through cell--cell contacts by a mechanism common to many other cell types. Relevant cell contacts would be influenced not only by the proportions of differ- ent types of cells and their products, but also by the total concentration of cells, the dose of antigen or stimulant used to initiate proliferation and the time allowed for the cellular interactions to occur. Lymphocytes may be subject to general growth control mecha- nisms applicable to cells in culture in addition to their special properties of responding to antigenic stimulation. Key words: lymphocyte stimulation -- helpel; and suppressor cells -- cell concentration INTRODUCTION Suitable assay systems for measuring the functions of lymphocyte sub- populations have not been developed as rapidly as the technology for identi- fication of lymphocyte subpopulations by surface markers. Discrepancies in the reported functions of cells identified by surface markers (Goodwin and 0022-1759/82/0000--0000/$02.75 © 1982 Elsevier Biomedical Press