Protein Design Labs, Inc.

Bioseek, Inc.

Rolf Ehrhardt

Kenneth Hong

Cary L Queen

Methods and compositions are provided for the creation and screening of non-human animal models having chronic inflammation. Immunocompromised host animals are injected with a population of immunocompetent effector cells, depleted of CD25&plus; T cells. The effector cells are tolerant of the host major histocompatibility antigens, but reactive to at least one antigen present in the host animal. The transferred cells are preferably stimulated and localized by administration of an immunostimulant at a local site. The animals are useful for a variety of screening assays and for investigation into disease causes and pathways. A variety of chronic inflammatory diseases may be studied with this model, including psoriasis, rheumatoid arthritis, diabetes, inflammatory bowel disease and multiple sclerosis.

Models of chronic and acute inflammatory diseases

Methods and compositions are provided for the creation and screening of non-human animal models having many of the histologic characteristics of human psoriasis. Immunocompromised host animals are injected with a purified population of CD45Rb positive cells, which are tolerant of the host major histocompatibility antigens, but are mismatched at one or more minor antigens. The injected cells are stimulated with a pro-inflammatory cytokine, e.g. IL-12, and a polyclonal activating agent. The injected animals develop a chronic skin disorder that includes histological features observed in human psoriasis, e.g. rete pegs, severe acanthosis and infiltration of Th1 cells into the dermis.

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San Francisco, CA, United States of America

Rolf Ehrhardt