The invention is based upon the discovery that T regulatory type 1 (Tr1) cells express particular cell surface markers that allow for their selection, enrichment, isolation, purification and administration. The ability to use the particular markers described herein to select, enrich, isolate, purify and administer Tr1 cells allows for improved methods of Tr1 therapies for treating a wide variety of diseases and disorders.

Described herein are compositions and methods for signaling and antigen-presenting bifunctional receptors (SABRs) comprising one or more antigen presenting domains; and one or more signal transduction domains, wherein the one or more antigen presenting domains comprise a binding fragment of a major histocompatibility complex (MHC) molecule. Various immunological functions of the SABRs are also described.

The present invention generally relates to the production of antigen-specific T regulatory cells (Tregs). Such cells can be used in therapy to minimize undesirable immune responses such as those observed in autoimmunity and hemophilia and other diseases as well as in the response to protein therapy for genetic diseases. Methods for producing antigen specific Tregs and conditions for preferential expansion of functionally stable, specific Tregs are also provided.

The present invention provides methods of enforcing expression of an E-selectin and/or L-selectin ligand on a surface of a cell. Also provided are methods of enabling and/or increasing binding of a cell to E-selectin and/or L-selectin, methods of increasing homing and/or extravasation in a population of transplanted cells, methods of producing modified cells, including stem cells, for transplanting into a subject, methods of treating or ameliorating the effects of a symptom, a disease or an injury in a subject, and methods for inducing and/or enhancing homing of a population of cells to a therapeutic target in a subject. The invention further provides pharmaceutical compositions comprising a population of cells produced by the methods of the invention and kits that include such compositions for treating or ameliorating the effects of a symptom, a disease or an injury in a subject.

The present disclosure relates to a soluble CD52 glycoprotein and its use in treating diseases regulated by effector T-cells, for example autoimmune diseases such as type 1 diabetes. The present disclosure also relates to fusion proteins comprising the soluble glycoprotein, to cells expressing high levels of CD52, and to diagnostic methods based on the detection of CD52 expression levels in a subject.

Provided by the disclosure are methods for modulating differentiation of regulatory T cells (e.g., CD4.sup.+ or CD8.sup.+ regulatory T cells). In some embodiments, methods include contacting regulatory T cells with an agent that decreases Helios activity and/or Helios expression.

The present disclosure relates to a soluble CD52 glycoprotein and its use in treating diseases regulated by effector T-cells, for example autoimmune diseases such as type 1 diabetes. The present disclosure also relates to fusion proteins comprising the soluble glycoprotein, to cells expressing high levels of CD52, and to diagnostic methods based on the detection of CD52 expression levels in a subject.

The invention provides, inter alia, immunoinhibitory glycosphingolipids and immunoinhibitory alpha-galactosylceramides and compositions and preparations thereof, and methods of use thereof including in the treatment of conditions characterized by increased iNKT cells and/or activity.

A method for treating inflammation and/or autoimmune diseases comprises administering to a subject in need thereof, a composition comprising a CDK8 inhibitor. In another aspect, a method for increasing IL-10 production comprises administering to a subject in need thereof a CDK8 inhibitor. In another aspect, a method for enhancing T.sub.reg cell differentiation, comprising administering a composition comprising a CDK8 inhibitor. In certain example embodiments, the subject suffers from an inflammatory bowel disease. In certain other example embodiments, the subject requires immunosuppression to prevent rejection following a transplantation procedure.

Methods for diagnosing and prognosing autoimmune diseases and T cell lymphomas are provided, for example by measuring levels of intracellular osteopontin (OPN-i). Also provided are screening methods for identifying activators and inhibitors of the transcription factor Bcl6, which is involved in T cell activation/differentiation. Other aspects of the disclosure provide methods for enhancing adoptive T cell transfer.