T cell growth factor-enhanced PHA response of human thymus cells: requirement for T3+ cells

Human thymocytes normally proliferate poorly in PHA-stimulated cultures, as measured by thymidine uptake. Their response increases when supernatant factors from mitogen-stimulated human lymphocyte cultures (SUP) are added. The cells that proliferate in PHA + SUP-stimulated cultures continue to divide if they are resuspended with fresh SUP every 3 to 4 days. PHA-stimulated thymocytes are deficient in the production of the T cell growth factor interleukin 2 (IL 2). The phenotype of thymocytes prior to stimulation was 90% T6+, 80% T4+, 83% T8+, and 12% T3+, whereas that of the cells after 3 days in culture with PHA + SUP was 1% T6+, 18% T4+, 66% T8+, and 80% T3+. Lysis of T3+ cells from the thymocyte preparation before culture greatly reduced the proliferative response to PHA + SUP. This suggests that the PHA-induced proliferation of more mature thymus cells is restricted by a lack of essential growth factors (either IL 1 or IL 2) and that the co-stimulating activity of SUP on human cells is predominantly on thymus cells that already are T3+.