Regulatory T cells (Treg) are engineered to express a chimeric antigen receptor (CAR), that specifically binds folate receptor beta; and are administered to an individual for treatment of inflammation at sites characterized by the presence of activated myeloid cells. Also provided are methods for utilized engineered T regulatory cells to enhance hematopoietic cell transplantation.

Methods and compositions are provided for combined transplantation of a solid organ and hematopoietic cells to a recipient, where tolerance to the graft is established through development of a persistent mixed chimerism. An individual with persistent mixed chimerism, usually for a period of at least six months, is able to withdraw from the use of immunosuppressive drugs after a period of time sufficient to establish tolerance.

The present disclosure provides distinct therapeutic populations of cells that form a pharmaceutical composition useful in hematopoietic stem/progenitor cell transplant. For example, the present disclosure provides a therapeutic population of cells, comprising an enriched population of hematopoietic stem/progenitor cells, memory T cells, regulatory T cells, and wherein the population of cells is depleted of na?ve conventional ??-T cells. The present disclosure further provides methods of treatment using the therapeutic population of cells. In other embodiments, the present disclosure provides methods of producing a therapeutic population of cells.

Materials and methods of treating a patient with type 2 diabetes mellitus, metabolic syndrome, obesity, infertility, high blood pressure, hyperthyroidism, and hypothyroidism, hyperlipidaemia, osteoporosis, osteoarthritis, hypoadrenalism, polycystic ovary syndrome, or Parkinson's disease comprising administering a therapeutically effective amount of ex vivo cultured activated peripheral blood mononuclear cells (PBMCs) to the patient. The ex vivo cultured activated cells are activated and cultured in a presence of a cytokine and may be autologous or allogeneic relative to the patient.

Mesenchymal stromal cells are engineered to express a chimeric antigen receptor (CAR), that specifically binds a marker of activated myeloid cells, including without limitation folate receptor beta; and are administered to an individual for treatment of inflammation at sites characterized by the presence of activated myeloid cells.

Embodiments of various aspects described herein are directed to methods and compositions for producing a tolerognic or immunosuppressive dendritic cell. In particular, an immunosuppressive dendritic cell can be produced by contacting a dendritic cell with an agent that stimulates the IL 27/ectonucleotidase CD39 axis signaling. In some embodiments, the methods and/or compositions described herein can be used for treating an autoimmune disease or disorder, e.g., but not limited to multiple sclerosis (MS) and type 1 diabetes.

The disclosed methods are generally directed to preventing, treating, suppressing, controlling or otherwise mitigating side effects of T-cell therapy, the T-cell therapy designed to accelerate immune reconstitution, induce a GVM effect, and/or target tumor cells.

The technology described herein is directed to compositions comprising components of multi-component CALs or CARs, e.g., a TCR recognition domain; and one or both of: (a) an intracellular signaling domain; and (b) a first-type protein interaction domain. Further provided herein are methods for treating or preventing an autoimmune disease, a transplant rejection, or graft versus host disease.

The invention provides a fusion protein for use in the treatment of HvG disease in a patient having received a transplant, for use in suppressing the host's immune response directed against the transplant. The fusion protein is adapted for use in suppressing the immune rejection of a transplant which contains or expresses HLA-A*02 or SLA-01*0401 in a recipient patient who is negative for HLA-A*02 or SLA-01*0401, i.e. the patient prior to transplantation does not express HLA-A*02 or SLA-01*0401. The fusion protein is a chimeric antigen receptor (CAR), which upon expression in regulatory T-cells (T.sub.reg) causes a specific suppressor activity of the regulatory T-cells in the presence of HLA-A*02 or SLA-01*0401.

The present invention describes a method of treating, preventing, reducing the likelihood of or alleviating a symptom of Alzheimer's disease and associated conditions by increasing OPN expression. The invention further provides for a method of improving cognitive function in a subject in need thereof.