Abstract: Method for the treatment of multiple sclerosis and other T cell mediated autoimmune disorders is described. The method involves administering to a subject a therapeutically effective amount of an antagonist of a receptor on a surface of a T cell which mediates contact dependent helper effector functions, for example, an anti-gp39 antibody.

Abstract: A method of treating graft-vs-host diseases by administration of bone marrow and an anti-gp39 antibody specific to human gp39 is provided.

Abstract: Methods for inducing T cell tolerance to a tissue or organ graft in a transplant recipeint are disclosed. The methods involve administering to a subject: 1) an allogeneic or xenogeneic cell which expresses donor antigens and which has a ligand on the cell surface which interacts with a receptor on the surface of a recipient T cell which mediates contact-dependent helper effector function; and 2) an antagonist of the receptor which inhibits interaction of the ligand with the receptor. In a preferred embodiment, the allogeneic or xenogeneic cell is a B cell, preferably a resting B cell, and the molecule on the surface of the T cell which mediates contact-dependent helper effector function is gp39. A preferred gp39 antagonist is an anti-gp39 antibody. The allogeneic or xenogeneic cell and the gp39 antagonist are typically administered to a transplant recipient prior to transplantation of the tissue or organ.

Abstract: Methods of suppressing a humoral immune response to a thymus-dependent (TD) antigen are disclosed. The methods involve administering to a subject a TD antigen with an antagonist of a molecule which mediates contact-dependent helper effector functions. In a preferred embodiment, the antagonist is an antagonist of gp39. Primary and secondary humoral immune responses can be suppressed and suppression is prolonged.

Abstract: Methods for inducing T cell tolerance to a tissue or organ graft in a transplant recipeint are disclosed. The methods involve administering to a subject: 1) an allogeneic or xenogeneic cell which expresses donor antigens and which has a ligand on the cell surface which interacts with a receptor on the surface of a recipient T cell which mediates contact-dependent helper effector function; and 2) an antagonist of the receptor which inhibits interaction of the ligand with the receptor. In a preferred embodiment, the allogeneic or xenogeneic cell is a B cell, preferably a resting B cell, and the molecule on the surface of the T cell which mediates contact-dependent helper effector function is gp39. A preferred gp39 antagonist is an anti-gp39 antibody. The allogeneic or xenogeneic cell and the gp39 antagonist are typically administered to a transplant recipient prior to transplantation of the tissue or organ.

Abstract: Antibodies that bind a protein gp39 (also referred to as CD40 ligand) are disclosed. Preferably, the antibodies are monoclonal antibodies of an IgG1 isotype and bind human gp39. In a preferred embodiment, an antibody of the invention binds an epitope recognized by a monoclonal antibody 24-31, produced by a hybridoma 24-31 (ATTC Accession No. HB11712) or binds an epitope recognized by a monoclonal antibody 89-76, produced by a hybridoma 89-76 (ATCC Accession No. HB 11713). Pharmaceutical compositions comprising the antibodies of the invention are also disclosed. The antibodies of the invention are useful for inhibiting B cell proliferation and differentiation, T cell responses and for inducing T cell tolerance. Nucleic acid molecules encoding anti-gp39 antibodies, or portions thereof, as well as expression vectors and host cells incorporating said nucleic acid molecules, are also encompassed by the invention.

Abstract: Methods for inducing antigen-specific T cell tolerance are disclosed. The methods involve contacting a T cell with: 1) a cell which presents antigen to the T cell, wherein a ligand on the cell interacts with a receptor on the surface of the T cell which mediates contact-dependent helper effector function; and 2) an antagonist of the receptor on the surface of the T cell which inhibits interaction of the ligand on the antigen presenting cell with the receptor on the T cell. In a preferred embodiment, the cell which presents antigen to the T cell is a B cell and the receptor on the surface of the T cell which mediates contact-dependent helper effector function is gp39. Preferably, the antagonist is an anti-gp39 antibody or a soluble gp39 ligand (e.g., soluble CD40). The methods of the invention can be used to induce T cell tolerance to a soluble antigen or to an allogeneic cell.

Abstract: Method for the treatment of multiple sclerosis and other T cell mediated autoimmune disorders is described. The method involves administering to a subject a therapeutically effective amount of an antagonist of a receptor on a surface of a T cell which mediates contact dependent helper effector functions, for example, an anti-gp39 antibody.

Abstract: Antibodies that bind a protein gp39 (also referred to as CD40 ligand) are disclosed. Preferably, the antibodies are monoclonal antibodies of an IgG1 isotype and bind human gp39. In a preferred embodiment, an antibody of the invention binds an epitope recognized by a monoclonal antibody 24-31, produced by a hybridoma 24-31 (ATTC Accession No. HB11712) or binds an epitope recognized by a monoclonal antibody 89-76, produced by a hybridoma 89-76 (ATCC Accession No.HB11713). Pharmaceutical compositions comprising the antibodies of the invention are also disclosed. The antibodies of the invention are useful for inhibiting B cell proliferation and differentiation, T cell responses and for inducing T cell tolerance. Nucleic acid molecules encoding anti-gp39 antibodies, or portions thereof, as well as expression vectors and host cells incorporating said nucleic acid molecules, are also encompassed by the invention.

Abstract: Methods for inducing T cell unresponsiveness to a tissue or organ graft in a transplant recipeint are disclosed. The methods involve administering to a subject: 1) an allogeneic or xenogeneic cell which expresses donor antigens and which has a ligand on the cell surface which interacts with a receptor on the surface of a recipient T cell which mediates contact-dependent helper effector function; and 2) an antagonist of the receptor which inhibits interaction of the ligand with the receptor. In a preferred embodiment, the allogeneic or xenogeneic cell is a B cell, preferably a resting B cell, and the molecule on the surface of the T cell which mediates contact-dependent helper effector function is gp39. A preferred gp39 antagonist is an anti-gp39 antibody. The allogeneic or xenogeneic cell and the gp39 antagonist are typically administered to a transplant recipient prior to transplantation of the tissue or organ.