Functional consequences of sheep red blood cell resetting for human T cells: Gain of reactivity to mitogenic factors

Phytohemagglutinin (PHA)‐stimulated human lymphocytes release soluble products which are mitogenic for other lymphocytes, so‐called mitogenic factors (MF). MF is highly mitogenic for peripheral T lymphocytes separated by rosetting with sheep red blood cells (SRBC), while being very poorly mitogenic for unseparated human peripheral lymphocytes. This lack of correlation between the magnitude of the responses and the number of T cells in these cell preparations was investigated. Peripheral T cells enriched by passage through nylon wool columns do not respond to MF. Unfractionated lymphoid preparations are strongly activated by MF once they have been exposed to SRBC, even without further enrichment for rosetteforming cells. Red cells from species other than sheep, which do not form rosettes with human T cells, are not capable of inducing responsiveness to MF. Lymphocytes exposed to PHA for 24 h become highly responsive to MF. We conclude from these results that rosetting of human T cells with SRBC has functional consequences and alters the reactivity of T cells to MF. Furthermore, these factors are not directly mitogenic for resting, unmodified T cells but rather to cells which have already been activated or modified in some way.