Method and compositions for the treatment of autoimmune disease using heat shock proteins

DETAILED DESCRIPTION OF THE INVENTION Methods and compositions for the treatment of autoimmune disease are described.
The invention is based, in part, on newly discovered treatment regimens which provide protection against autoimmune disease.
The treatment regimens comprise the administration of hsps, optionally complexed noncovalently with antigenic molecules.
The hsps administered in accordance with the invention are ideal interventional agents against autoimmunity.
In specific embodiments, such administered hsps 1) trigger protective immunoregulatory mechanisms effective when administered after the onset of autoimmune damage and, therefore, are immunotherapeutic, as opposed to prophylactic; 2) are effective for long-term protection; 3) effect antigen-specific immune suppression via antigen presenting cells (APCS) which trigger production of suppressor CD4+ C.
ells that inactivate autoreactive T cells; 4) have a more general effect than individual administered autoantigens, and thus do not require identification of individual autoantigens for effectiveness; 5) nonetheless, have an effect that is specific to at least a substantial portion of the autoantigens that activate autoreactive T cells; 6) are less physiologically disruptive than such non-specific agents as cytokines, because the effect of hsps on the cytokine milieu is mediated through the endogenous, local, cellular response instead of systemically; 7) are of mammalian origin; and 8) are adjuvant free.
Administration of hsps in accordance with the methods described below are a novel immunotherapeutic modality, ideal for the treatment of autoimmune diabetes and other autoimmune diseases as well.
In addition, the hsp-based immunotherapeutic methods detailed below are useful for prevention and treatment of rejection of transplanted tissues or organs, such as tissues transplanted to replace those being damaged by autoimmune disease, including but not limited to transplanted islet cells to treat IDDM.
In accordance with the invention, hsps, either uncomplexed or complexed with antigenic molecules, are administered to provide therapeutic treatment or, alternatively, prophylactic protection of autoimmune disease