Two distinct factors are required for induction of T-cell growth

The molecular and cellular basis of T-lymphocyte activation remains a central question in immunology. The growth of already proliferating T cells is known to depend on T-cell growth factor (TCGF), a physiological mitogen. Noncycling T lymphocytes, however, are not sensitive to TCGF. They require a short contact with mitogenic lectins, such as concanavalin A (Con A) or leukoagglutinin to bind and respond to TCGF, and will thereafter maintain exponential growth for long periods provided that TCGF is not limiting. While the induction of TCGF reactivity results from the direct contact of Con A with resting T cells, the lectin-dependent production of TCGF is known to involve two cell types, both present in mouse spleen. One consists of I-A-negative cells, most of which are Thy-1-positive T lymphocytes, and the other consists of I-A-positive, immunoglobulin-negative, Thy-1-negative cells, most of which are macrophages. The nature of the respective contributions of the two cell types, and in particular the cellular origin of TCGF, has not yet been established. We have now established the I-A-negative population as the source of TCGF and show here that macrophages are required to supply a 20,000-molecular weight factor, chemically and functionally distinct from TCGF, which supports the production of TCGF by the I-A-negative cells.