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Study on regulatory T Treg cells has opened a new paradigm in immunology because of potential benefit for treating immunological diseases and providing some clues for central issues of immunology about tolerance. We report here a newly identified Treg cell line, termed HOZOT, which exhibits not only suppressor activity but also cytotoxic and even, under certain conditions, helper activities.
Another function, cytotoxic activity is equally observed toward mouse cell lines and human tumor cell lines, where killing mechanisms are distinct from each other. In conclusion, HOZOT should be categorized as a novel T cell subset according to its multifunctional property and we propose to designate such multifunctional T cell subset as Tchreg c ytotoxic, h elper, and reg ulatory T cell. Analyses on Tchreg cells would provide a new layer of knowledge in T cell biology. We hypothesise that Tregs may also control DC expression of co-stimulatory molecules in vivo in the steady state.
No increase in expression of any of the molecules studied was observed for thymic DCs. Our data indicate that transferred Tregs down-regulated expression of CD80 and CD86 to the normal levels present in immuno-competent mice. We are currently investigating the molecules involved in this process. Overexpression of co-stimulatory molecules in immunodeficient hosts lacking Treg cells may thus contribute to the lymphopaenia-induced proliferation LIP response previously attributed to increased availability of cytokines, or to reduced competition for self-peptide:MHC complexes.
Therefore, we designated such multifunctional T cells as Tchreg cytotoxic, helper, and regulatory T cells. To investigate underlying mechanisms of HOZOT induction, we have newly developed a reproducible and efficient induction system. This culture consists of three steps. Regulatory property was obtained through step 2 and 3. Since this culture system is more reproducible and efficient than the original method, where unpurified cord blood mononuclear cells were used, we have been identifying key molecules involved in Tchreg cell induction by exploiting this system.
