Allogeneic cellular immunotherapy for opportunistic infection
A method for stimulating the immune system in immunocompromised patients in order to treat opportunistic infection. The method involves the infusion of intentionally mismatched allogeneic cells. In order to prevent graft vs. host disease complications, the allogeneic cells can be irradiated prior to infusion.
1. A method of generating a de-novo Th1 anti-pathogen immunity in a host comprising:
inducing expression of Th1 cytokines by administering allogeneic, activated Th1-cells wherein the allogeneic cells are T-cells that have not been exposed to the pathogen, are activated through CD3/CD28 cell surface moieties, irradiated and HLA-mismatched to the host, wherein the host is immunosuppressed, has a Th2-biased immunity and is susceptible to or has developed an opportunistic infection by the pathogen due to immunosuppression;
maintaining the Th1 cytokine environment during the activation of innate immune effector cells and until establishment of an anti-pathogen Th1 adaptive immune response developed by the host immune response.
2. The method of claim 1 wherein the innate immune effector cells comprise NK cells and DC.
3. The method of claim 1 wherein the allogeneic cells are administered intravenously.
4. The method of claim 1 wherein the maintaining comprises administration of additional allogeneic cells.
5. The method of claim 4 wherein the additional allogeneic cells are administered intradermally or intravenously.
6. The method of claim 1 wherein the maintaining comprises administration of allogeneic cells and pathogen antigens.
7. The method of claim 1 wherein the pathogen is a member of the genus Aspergillus.
8. The method of claim 1 wherein the inducing and maintaining are performed without exacerbating GVHD in the host.
9. The method of claim 1 , wherein the T-cells express high density of CD40L.