Mechanism of T cell activation I. A screening of “step one” ligands

Abstract

A number of ligands which bind to T cell surfaces were screened on murine spleen cells for their functional ability to induce either of the two necessary steps in the process of T cell triggering: (a) expression of growth receptors by T lymphocytes and (b) production of T cell growth factors in cultures containing both T cells and accessory cells. Among four lectins tested, concanavalin A was found to induce both responses but is primarily a “step 2” ligand, in particular at low concentrations; leucoagglutinin was the most potent “step 1” ligand with very limited “step 2” activity; wheat germ agglutinin and soybean lectin were inactive. Direct mitogenicity of the lectin to normal spleen cell cultures was limited by the poorest of these two functional properties. A number of rabbit anti‐lymphocyte antisera, anti‐Thy‐1 alloantisera, anti‐H‐2 and anti‐Ia monoclonal antibodies, as well as complexes of rabbit IgG, were all found to be devoid of “step 1” activity, and consequently, non‐ mitogenic for spleen cells. In contrast, a rabbit anti‐mouse brain antiserum, although also devoid of mitogenicity, was found to be capable of “step 1” induction. These results suggest that not all rearrangements of T cell surface membrane components upon binding of a ligand result in the functional expression of growth receptors. This appears to be the result of selective interactions with specific sites which include structures binding to concanavalin A, leucoagglutinin and rabbit anti‐mouse brain antibodies.

Effect of interleukin 1 on human thymocytes and purified human T cells.

“…The implication of these studies is that IL-1 modulates T cell proliferation by regulating the production oflL-2 (18). IL-2 has therefore been proposed as the ultimate mitogen regulating cell division (25). Studies are currently underway attempting to correlate the production of IL-2 in the human system, and the subsequent induction of cell division to determine whether this lymphokine and lymphocyte proliferation are invariably linked.…”

A synaptic basis for T-lymphocyte activation

“…The final physiological effect depends directly on the number of receptors which are bound or occupied and then subsequently crosslinked. Low levels of cross-linking, usually with antibody alone as shown with anti-Thy-1, anti-T3 and anti-clonotypic antibodies, activates only IL-2 receptor expression, while higher levels are required for IL-2 production [4,13,14]. Regulation of activation can therefore be accomplished by controlling the amount of cross-linking.…”

Kinetics of cellular oncogene expression in mouse lymphocytes: I. Expression of c‐myc and c‐rasHa in T lymphocytes induced by various mitogens

“…Thediffercnces found in total Tcell populations regarding the kinetics of c-myc gene expression after Con A and LA activation can thus in part be explained by the different T cell subpopulations addressed. While Con A stimula.tes both Lyt-2-and Lyt-2+ T cells, LA at tbe concentrations used only activates Lyt-2+ ceUs [12). The latter display tbeir peculiar kinetics of c-myc gene expression cven after Stimulation with Con A.…”

“…Stimulation by Con A Ieads to (a) the expression of IL2 receptors; (b) production and secretion of IL2, particularly by helper T cells and (c) proliferation of both helper and cytotoxic T cells [17]. Stimulation by low doses of LA only results in tbc expression of IL2 reccptors but insufficient production of IL2 (12]. These cells thercfore proliferate only upon addition of IL2.…”