Abstract: Described herein are methods and transplant compositions for promoting or inducing organ transplant tolerance and/or immune tolerance by conditioning a recipient with radiation-free, low-doses of cyclophosphamide (CY), pentostatin (PT), and anti-thymocyte globulin (ATG) prior to transplantation of PD-L1+ donor-derived CD4+ T-depleted bone marrow cells. In certain embodiments, the methods may also include transplanting an organ, such as a solid organ, into the recipient. The transplant compositions may comprise a therapeutically effective amount of PD-L1+ donor-derived CD4+ T-depleted bone marrow cells and a donor organ.

Abstract: Disclosed herein are conditioning regimens and methods for inducing MHC- or HLA-mismatched mixed chimerism by conditioning a recipient with radiation-free, low-doses of cyclophosphamide (CY), pentostatin (PT), and anti-thymocyte globulin (ATG) prior to transplantation of donor bone marrow cells. In certain embodiments, the donor bone marrow cells may be CD4+ T-depleted bone marrow cells. The conditioning regimens and methods may also include administering one or more populations of conditioning donor cells selected from donor CD4+ T-depleted spleen cells, donor CD8+ T cells, and donor G-CSF-mobilized peripheral blood mononuclear cells. The conditioning regimen is clinically acceptable and can be used for treating hereditary hematological diseases and autoimmune diseases, as well as for promoting organ transplantation immune tolerance.

Abstract: Disclosed is a method of preventing or treating acute GVHD (aGVHD) such as gut aGVHD, steroid-resistant aGVHD, and steroid-resistant gut aGVHD in a subject receiving a hematopoietic cell transplantation (HCT) or autoimmune colitis by administering to the subject an effective amount of an anti-IL-22 antibody, an anti-IL-6 antibody, donor-type CX3CR1hi MNPs, donor-type NK cells, a ceacam-1 antagonist, an anti-Gr-1 antibody, or a combination thereof.

Abstract: Disclosed is a method of preventing or treating GVHD while preserving GVL activity in a subject receiving a hematopoietic cell transplantation (HCT) by administering to the subject an effective amount of an anti-IL-2 antibody such as an anti-IL-2-JES6 antibody.

Abstract: Disclosed are methods of treating or preventing autoimmune diseases by inducing haploidentical mixed chimerism and condition regimen for by inducing haploidentical mixed chimerism.

Abstract: Disclosed herein are conditioning regimens and methods for inducing MHC- or HLA-mismatched mixed chimerism by conditioning a recipient with radiation-free, low-doses of cyclophosphamide (CY), pentostatin (PT), and anti-thymocyte globulin (ATG) prior to transplantation of donor bone marrow cells. In certain embodiments, the donor bone marrow cells may be CD4+ T-depleted bone marrow cells. The conditioning regimens and methods may also include administering one or more populations of conditioning donor cells selected from donor CD4+ T-depleted spleen cells, donor CD8+ T cells, and donor G-CSF-mobilized peripheral blood mononuclear cells. The conditioning regimen is clinically acceptable and can be used for treating hereditary hematological diseases and autoimmune diseases, as well as for promoting organ transplantation immune tolerance.

Abstract: Disclosed herein are conditioning regimens and methods for inducing MHC- or HLA-mismatched mixed chimerism by conditioning a recipient with radiation-free, low-doses of cyclophosphamide (CY), pentostatin (PT), and anti-thymocyte globulin (ATG) prior to transplantation of donor bone marrow cells. In certain embodiments, the donor bone marrow cells may be CD4+ T-depleted bone marrow cells. The conditioning regimens and methods may also include administering one or more populations of conditioning donor cells selected from donor CD4+ T-depleted spleen cells, donor CD8+ T cells, and donor G-CSF-mobilized peripheral blood mononuclear cells. The conditioning regimen is clinically acceptable and can be used for treating hereditary hematological diseases and autoimmune diseases, as well as for promoting organ transplantation immune tolerance.

Abstract: Disclosed herein are methods of preventing and treating GVHD and autoimmune diseases. The methods entail administering one or more doses of an effective amount of a therapeutic agent to a subject to in vivo knock down Stat3 in the T cells and/or B cells of the subject. Alternatively, the methods entail contacting donor T cells and/or B cells with an effective amount of a therapeutic agent to in vitro knock down Stat3 and administering the Stat3-deficient T cells and/or B cells to the subject. Some examples of the therapeutic agent include small molecule Stat3 inhibitors such as Stat3 siRNAs delivered by an antibody to specifically knock down Stat3 in the lymphocytes of the target tissue.

Abstract: Disclosed herein are methods of preventing and treating acute GVHD and chronic GVHD after hematopoietic cell transplantation (HCT), as well as methods of in vivo augmenting expansion of donor CD8+ T cells in the lymphoid tissues in vivo after HCT and methods of augmenting recipient tissue expression of programmed death-ligand 1 (PD-L1, or B7H1) after HCT. The methods entail administering one or more doses of an effective amount of a therapeutic agent to a recipient simultaneously, immediately before, or immediately after HCT to temporarily deplete CD4+ T cells or to reduce serum IL-2. Some examples include an anti-CD4 antibody or an anti-CD4-meditope-immunotoxin, an anti-IL-2 antibody, an agent blocking IL-2R, and/or a PD-L1-Ig. One or more additional therapeutic agents such as IFN- can be administered.

Abstract: Disclosed herein are methods for treating type 1 diabetes by reversing autoimmunity and replenishing beta cells. More specifically, type 1 diabetes is treated by administering exogenous Sox9+ cells and a low dose of gastrin and epidermal growth factor (GE) under hyperglycemia or medium hyperglycemia condition during or after induction of mixed chimerism in a subject.

Abstract: Disclosed herein are conditioning regimens and methods for inducing MHC- or HLA-mismatched mixed chimerism by conditioning a recipient with radiation-free, low-doses of cyclophosphamide (CY), pentostatin (PT), and anti-thymocyte globulin (ATG) prior to transplantation of donor bone marrow cells. In certain embodiments, the donor bone marrow cells may be CD4+ T-depleted bone marrow cells. The conditioning regimens and methods may also include administering one or more populations of conditioning donor cells selected from donor CD4+ T-depleted spleen cells, donor CD8+ T cells, and donor G-CSF-mobilized peripheral blood mononuclear cells. The conditioning regimen is clinically acceptable and can be used for treating hereditary hematological diseases and autoimmune diseases, as well as for promoting organ transplantation immune tolerance.

Abstract: Prevention of autoimmune disease and induction of transplantation tolerance in a recipient can be achieved by induction of mixed chimerism via bone marrow transplantation (BMT), but this procedure requires total body irradiation (TBI)-conditioning of the recipient. The toxicity of radiation and potential for graft versus host disease (GVHD) prevents its clinical application. Donor CD8+ T cells play a critical role in facilitation of engraftment, but also contribute to induction of GVHD in TBI-conditioned recipients. It is disclosed herein that high doses of donor CD8+ T cells in combination with donor bone marrow (BM) cells induces mixed chimerism without GVHD in recipients conditioned with anti-CD3 mAb. These chimeric recipients display donor specific tolerance and reversal of insulitis. These results establish that donor CD8+ T cell-mediated facilitation of engraftment can be separated from GVHD in non-irradiated recipients.

Abstract: Allogeneic hematopoietic cell transplantation (HCT) is an effective therapy for treatment of hematological malignancies and various autoimmune conditions. However, HCT traditionally requires conditioning by total body irradiation and/or chemotherapy, both of which are toxic and induce GVHD. Provided herein are compositions and methods for conditioning a subject for HCT by administering one or more anti-CD3 compounds and one or more histone deacetylase inhibitors. Also provided herein are methods for reducing GVHD in a subject receiving total body irradiation prior to HCT comprising administering one or more anti-CD3 compounds to the subject prior to total body irradiation.

Abstract: Pathogenic polyclonal B cell activation and immunoglobulin class switching to pathogenic autoantibodies is inhibited by binding molecules that specifically interfere with CD1 antigen, but do not activate signaling (blocking agents), or by molecules that bind to the T cell antigen receptor on T cells that recognize CD1. When CD1 mediated signaling is thus blocked, the T cell response is diminished, resulting in reduced polyclonal B cell activation and reduced immunoglobulin class switching to pathogenic autoantibodies.

Abstract: Graft versus host disease (GVHD) may be prevented, while preserving a beneficial by graft versus leukemia (GVL) effect, in a subject receiving an allogeneic hematopoietic cell transplant by preconditioning the subject with a CD3 modulator, such as an agonistic anti-CD3 antibody. More than one CD3 modulator may be administered at one time. This method may be performed alone or in conjunction with irradiation of the subject. The use of anti-CD3 to precondition a subject to reduce tissue release of chemokines and prevents tissue dendritic cell migration to draining lymph nodes is also provided. Anti-CD3 preconditioning may also be used to modulate host dendritic cells before hematopoietic cell transplantation.

Abstract: Allogeneic hematopoietic cell transplantation (HCT) is an effective therapy for treatment of hematological malignancies and various autoimmune conditions. However, HCT traditionally requires conditioning by total body irradiation and/or chemotherapy, both of which are toxic and induce GVHD. Provided herein are compositions and methods for conditioning a subject for HCT by administering one or more anti-CD3 compounds and one or more histone deacetylase inhibitors. Also provided herein are methods for reducing GVHD in a subject receiving total body irradiation prior to HCT comprising administering one or more anti-CD3 compounds to the subject prior to total body irradiation.

Abstract: Prevention of autoimmune disease and induction of transplantation tolerance in a recipient can be achieved by induction of mixed chimerism via bone marrow transplantation (BMT), but this procedure requires total body irradiation (TBI)-conditioning of the recipient. The toxicity of radiation and potential for graft versus host disease (GVHD) prevents its clinical application. Donor CD8+ T cells play a critical role in facilitation of engraftment, but also contribute to induction of GVHD in TBI-conditioned recipients. It is disclosed herein that high doses of donor CD8+ T cells in combination with donor bone marrow (BM) cells induces mixed chimerism without GVHD in recipients conditioned with anti-CD3 mAb. These chimeric recipients display donor specific tolerance and reversal of insulitis. These results establish that donor CD8+ T cell-mediated facilitation of engraftment can be separated from GVHD in non-irradiated recipients.

Abstract: Prevention of autoimmune disease and induction of transplantation tolerance in a recipient can be achieved by induction of mixed chimerism via bone marrow transplantation (BMT), but this procedure requires total body irradiation (TBI)-conditioning of the recipient. The toxicity of radiation and potential for graft versus host disease (GVHD) prevents its clinical application. Donor CD8+ T cells play a critical role in facilitation of engraftment, but also contribute to induction of GVHD in TBI-conditioned recipients. It is disclosed herein that high doses of donor CD8+ T cells in combination with donor bone marrow (BM) cells induces mixed chimerism without GVHD in recipients conditioned with anti-CD3 mAb. These chimeric recipients display donor specific tolerance and reversal of insulitis. These results establish that donor CD8+ T cell-mediated facilitation of engraftment can be separated from GVHD in non-irradiated recipients.

Abstract: Pathogenic polyclonal B cell activation and immunoglobulin class switching to pathogenic autoantibodies is inhibited by binding molecules that specifically interfere with CD1 antigen, but do not activate signaling (blocking agents), or by molecules that bind to the T cell antigen receptor on T cells that recognize CD1. When CD1 mediated signaling is thus blocked, the T cell response is diminished, resulting in reduced polyclonal B cell activation and reduced immunoglobulin class switching to pathogenic autoantibodies.