Development of CD4+ T cell lines that suppress an antigen-specific immune response in vivo.

SUMMARY It has been suggested for many years that the regulation of the immune system for the maintenance of peripheral tolerance may involve regulatory/supressor T cells. In the past few years, several investigators have demonstrated that these cells can be generated in vitro . It has also been shown that they can inhibit the progression of various autoimmune disease models when infused into susceptible mice. We have generated two murine T cell lines in the presence of KLH-specific T cell clones from BALB/c or DBA2 mice. The lines are characterized by a low proliferative response to mitogens, the capacity to secrete high amounts of IL-10 and TGF-β , and small amounts of IFN-γ . Interestingly, these cells are unable to produce IL-2, IL-4 or IL-5. The study of the surface phenotype of both lines revealed CD4+ , CD25high , CD44low and CTLA-4– cells. When injected intravenously in (CBy.D2) F1 mice, these cells were able to inhibit 50–100% of the TNP-specific antibody production, when the hapten was coupled to KLH. In the present study we offer another evidence for the existence of regulatory T cells in the T lymphocyte repertoire, suggesting that they can also regulate immune responses to foreign antigens. Furthermore, we demonstrate an alternative pathway to generate these cells different from approaches used thus far. [ABSTRACT FROM AUTHOR]