Anchorage and lymphocyte function II. Contact with non-cellular surfaces, cell density and T-cell activation.

Varying numbers of human blood lymphocytes were stimulated by concanavalin A (Con-A) in a constant medium volume. At 'low' cell densities DNA synthesis was proportional to the number of cells in the cultures whereas at 'high' densities DNA synthesis was considerably lower than expected. In the presence of non-mitogenic microcarrier beads, (diameter 195 micrometer) to which the cells attached, DNA synthesis was proportional or nearly proportional to the cell number in the cultures also at 'high' cell densities. The potentiating effect of beads on lymphocyte stimulation was particularly noteworthy in individuals showing a weak mitogen response. Another approach that yielded proportionality between DNA synthesis and cell number both at 'low' and 'high' cell densities was the use of culture vessels with a larger bottom area. Under such conditions the presence of beads did not augment DNA synthesis. These results suggest that the availability of non-cellular adhesive surface is a major limiting factor and cell density a major regulating factor in the control of lymphocyte activation. Anchorage of the cells to a surface may modulate the density dependent 'growth control mechanism' indirectly via an influence on cell-cell interaction. An alternative less-likely interpretation is that the contact with non-cellular surfaces directly gives rise to regulatory responses in lymphocytes or accessory cells.