The regeneration of functional immune organ will be one of major focus in future immunology research. It will be an useful tool which induces efficient immune responses in the body on demand and offers effective ways to restore the immune status and treat uncontrollable obstinate diseases such as cancer, autoimmune diseases, severe infection and immuno-insufficiency/deficiency caused by tissue damages, abnormality, primary defect and aging. Artificially synthesized lymphoid organs may also provide us with a highly informative method not only for clinical aim but also basic study on the development and functions of immunological tissues and organs. We first reported successful generation of artificiallyconstructed lymph node-like tertiary lymphoid tissues at ectopic sites in mouse by applying certain stromal cell lines (Suematsu S, Watanabe T. Nat Biotechnol 22 (11):422-428, 2010). They showed a remarkable ability to induce immune responses upon antigen stimulation, especially when transplanted into naïve or immune-compromised hosts. In this review, we discuss about the rationale and method for the synthesis of functional tertiary lymph node-like lymphoid tissues in mouse. Especially, we discuss here on the method with applying only soluble factors but without using any stromal cell, that enables proper accumulation and functional organization of immune cells in grafts.