Ligand-Activated T Cell Growth Factor-Induced Proliferation: Absorption of T Cell Growth Factor by Activated T Cells

G. D. Bonnard; K. Yasaka; D. Jacobson

Abstract

The fate in culture of the T cell growth factor (TCGF), which is required for continued growth of human cultured T cells (CTC) in vitro, was studied. TCGF activity was stable for 7 days at 37°C. However, it was no longer detectable after incubation with actively growing CTC at 37°C for 3 days. This loss of TCGF activity also occurred quite rapidly and was detectable within 1 hr of incubation of 0.3 ml supernatant with 2 to 5 × 10⁷ CTC at 23°C. 2 × 10⁸ mononuclear peripheral blood leukocytes were not effective in removing TCGF activity, and incubation with similar numbers of cells from B and T cell lines had no effect. Three-day-old concanavalin A and phytohemagglutinin blasts were very reactive with TCGF, so that 10⁷ or 2 × 10⁷ cells consistently removed TCGF activity. These experiments suggested specific absorption of TCGF by activated T cells, and led us to develop a model of ligand-activated TCGF-induced proliferation of T cells: Ligands induce production of TCGF by T-producer cells and deliver a first signal to the T-responder cells. This causes a receptor for TCGF to appear on T-responder cells. Only then does TCGF deliver the obligatory second signal that is needed to drive the T-responder cells into proliferation.

Footnotes

↵² On leave of absence from the Division of Pathology (Chairman: Dr. J. C. Machado), Butantan Institute, San Paulo, Brazil.
↵¹ This model was first presented in March 1978 at the Symposium on Human Lymphocyte Differentiation in Montpellier (1), and later at the 12th Leukocyte Culture Conference in Beersheba (2). The factor(s) has also been called “mitogenic factor” in our previous publications, and our model “ligand-activated mitogenic factor-induced proliferation,” or “LAMP model,” in Reference 2. More recently, several groups, including ours, have preferred the designation “T-cell growth factor.”