|Title:|| Compositions and methods of using compositions with accelerated lymphocyte homing immunosuppressive properties|
|Abstract:||The methods and compositions of the invention and the compounds used in the invention involve a novel immunosuppression mechanism, accelerated lymphocyte homing immunosuppression (ALH-immunosuppression). For example, the compound FTY720 specifically directs lymphocytes to the peripheral lymph nodes, mesenteric lymph nodes, and Peyer's patches. By reversibly sequestering lymphocytes in these tissues, the compounds can inhibit an immune response in a mammal. Understanding these mechanisms provides a novel immunosuppression therapy that can synergistically interact with other immunosuppressive compounds. Screening methods for identifying similar ALH-immunosuppression compounds are also described. The invention allows better treatments and therapies wherever an immunosuppression regimen is desired.|
|Inventor(s):|| Chiba; Kenji (Fukuoka, JP), Adachi; Kunitomo (Fukuoka, JP) |
|Assignee:|| Mitsubishi Pharma Corporation (Osaka, JP) |
|Filing Date:||Jun 15, 1999|
|Claims:||1. A method for identifying the presence or absence of accelerated lymphocyte homing immunosuppressive activity in a sample comprising: providing a mammal with transplanted tissue or cells, administering the sample to the mammal, assaying for the survival of the transplanted tissue or cells in the mammal following the administration, and assaying for the amount of circulating blood lymphocytes to the amount of lymphocytes in peripheral or mesenteric lymphoid tissue in the mammal; wherein a decrease in the amount of circulating blood lymphocytes and an increase in the amount of lymphocytes in the peripheral or mesenteric lymphoid tissue indicates the presence of accelerated lymphocyte immunosuppressive homing activity, and wherein the absence of a decrease in the amount of circulating blood lymphocytes and the absence of an increase in the amount of lymphocytes in the peripheral or mesenteric lymphoid tissue indicates the absence of accelerated lymphocyte immunosuppressive homing activity. |
2. A method as claimed in claim 1, wherein the mammal is a rodent.
3. A method as claimed in claim 2, wherein the transplanted tissue is selected from the group consisting of heart, skin, or kidney.