Immune regulation

Abstract

A method of regulating the immune system of a subject that involves removing antigen presenting cells from subject and loading preselected class II peptide fragments onto the subjects APC's outside the body of the subject.

Description

RELATED APPLICATIONS [0001] This application claims the benefit of U.S. Provisional Application Ser. No. 60 / 361,136, filed Mar. 1, 2002, the contents of which are incorporated herein by reference in their entirety.TECHNICAL FIELD [0002] This invention relates to tissue and organ transplantation. BACKGROUND [0003] Since their discovery, the function of MHC class II genes has been associated with immune regulations. Although conclusions drawn from structural studies on class II heterodimers have primarily confined their role to that of presentation of antigenic peptides along with the class I molecules, numerous studies have indicated that class II proteins and / or their processed peptides should not only be regarded as histocompatibility antigens, i.e. targets of immune reactions. [0004] The development of numerous autoimmune diseases is associated with particular class II alleles although the specific implication of these class II alleles on either the presentation of self-antigenic ...

AI Technical Summary

Benefits of technology

[0007] Accordingly, the invention features a method of regulating the immune system of a subject, e.g., a human. The method includes: providing antigen presenting cells (APC) from the subject; loading preselected class II peptide fragments onto the subjects APC's outside the body of the subject; and introducing the loaded cells into the subject, thereby regulating the immune response of the subject.

[0028]“Loaded recipient antigen presenting cell (LRAPC),” as used herein, refers to APC's from a subject which presents selected peptides. A selected peptide is one which will modulate the immune response of the recipient, e.g., increased proliferation of T-reg's or donor graft acceptance.

[0036]“Help reduction”, as used herein, means the reduction of T cell help by the inhibition of the release of at least one cytokine, e.g., any of IL-2, IL-4, IL-6, gamma interferon, or TNF, from T cells of the recipient at the time of the first exposure to an antigen to which graft acceptance is desired. The inhibition induced in a recipient's T cell secretion of a cytokine must be sufficient such that the recipient is tolerized to an antigen which is administered during the reduction of help. Although not being bound by theory, it is believed that the level of reduction is one which substantially eliminates the initial burst of IL-2 which accompanies the first recognition of a foreign antigen but which does not eliminate all mature T cells, which cells may be important in educating and producing graft acceptance.

Problems solved by technology

Broadening the spectrum of potential graft donors, by using donor / recipient pairs matched for class II loci would be highly desirable in clinical transplantation, but unfortunately cannot be achieved due to the extreme structural diversity of class II molecules.

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