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

Abstract

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 mitogen¹. Noncycling T lymphocytes, however, are not sensitive to TCGF². They require a short contact with mitogenic lectins, such as concanavalin A (Con A)³ or leukoagglutinin⁴ to bind and respond to TCGF, and will thereafter maintain exponential growth for long periods provided that TCGF is not limiting⁵. While the induction of TCGF reactivity results from the direct contact of Con A with resting T cells³, the lectin-dependent production of TCGF is known to involve two cell types, both present in mouse spleen^1,3,6,7. One consists of I- A-negative cells, most of which are Thy-1-positive T lymphocytes^1,3, and the other consists of I-A-positive, immunoglobulin-negative, Thy-1-negative cells, most of which are macrophages^1,3. 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.