Mary L. Hilfiker

The biochemistry, biology, and role of interleukin 2 in the induction of cytotoxic t cell and antibody-forming b cell responses.

Interleukin 2 (IL 2) (Aarden et at. 1979) is a genetically unrestricted, soluble immunoenhancing factor which is produced by helper T cells following stimulation with either T cell mitogens or allogeneic cells. Presumably, IL 2 is also produced and secreted following specific antigen stimulation, although this question has not been carefully evaluated. The definitive biological assay for IL 2 measures the factors ability to maintain the growth of factor-dependent cytotoxic T cell lines. However, a broad spectrum of biological activities has been ascribed to IL 2. The factor has been reported to induce thymocyte proliferation either in the presence (Chen & DiSabato 1976, Paetkau et al. 1976) or absence (Farrar et al. 1978) of a suboptimal concentration of T cell mitogen. Additionally, IL 2 has been shown to augment the proliferation and generation of cytotoxic cells by alloantigenstimulated T cell populations (Wagner & Rollinghoff 1978, Farrar et al. 1978) and, in the process, induce the synthesis of immune interferon (IFNji) by the alloantigen-stimulated T cells (Farrar et al. 1981a). IL 2 has also been reported

Interleukin 2 activity of human intestinal mucosa mononuclear cells. Decreased levels in inflammatory bowel disease.

Interleukin 2, a soluble product of activated T lymphocytes, is of central importance in the development of an appropriate T-cell immune response. Defects in the production of or response to this lymphokine have been described in a variety of immune deficiency and autoimmune states, thus suggesting a role in the pathogenesis of such disorders. To investigate potential abnormalities of interleukin 2 in inflammatory bowel disease, we measured its activity in cultures of intestinal mucosa mononuclear cells derived from Crohns disease and ulcerative colitis patients. Lamina propria mononuclear cells from inflamed and control tissues were incubated with phorbol myristate acetate, and the amount of the lymphokine in the supernatants was quantitated in a biological assay using cloned, interleukin 2-dependent, cytotoxic mouse T-cell lines. We found that, in culture supernatants of cells from both forms of inflammatory bowel disease, interleukin 2 levels were significantly lower than those detected in cultures containing cells from histologically normal mucosa. Low levels were not correlated to duration, clinical activity, and anatomical location of the disease process or corticosteriod therapy. Deficient activity of this essential growth factor could contribute to abnormal T-cell proliferation and clonal expansion at the gut mucosal level, perhaps inducing a defective immune response leading to a chronic inflammatory reaction in Crohns disease and ulcerative colitis.

Phorbol myristic acetate enhances the production of interleukin 2.

Abstract Interleukin 2 is an antigen-nonspecific factor produced by Concanavalin A (Con A)-activated mouse spleen cells that has a number of biologic activities including the capacity to stimulate thymocyte proliferation, support the growth of continuous T cell lines, augment the antibody response of nude mouse spleen cells, and support the generation of antigen-specific cytotoxic T cells. In order to obtain increased amounts of Interleukin 2 for further purification and biologic studies, we have examined the use of Phorbol Myristic Acetate (PMA) as a costimulant. In this report we demonstrate that the addition of PMA to Con A-induced mouse spleen cell cultures results in a 5- to 20-fold increase in the production of Interleukin 2 activity under serum-containing and serum-free culture conditions.