NOD mice

Cell biology

Biotechnology

Biology

Autoimmunity

T cell

Regulatory T cell

Biochemistry

Phosphorylation

Immunology

B cell

In vivo

Immune system

In vitro

Autoimmune disease

IL-2 receptor

Immune tolerance

Experimental autoimmune encephalomyelitis

Medicine

Immunotherapy

STAT5

Regulatory B cells

Antibody

Nature Medicine

Interleukin-2 (IL-2) has been shown to suppress immune pathologies by preferentially expanding regulatory T cells (Tregs). However, this therapy has been limited by off-target complications due to pathogenic cell expansion. Recent efforts have been focused on developing a more selective IL-2. It is well documented that certain anti-mouse IL-2 antibodies induce conformational changes that result in selective targeting of Tregs. We report the generation of a fully human anti-IL-2 antibody, F5111.2, that stabilizes IL-2 in a conformation that results in the preferential STAT5 phosphorylation of Tregs in vitro and selective expansion of Tregs in vivo. When complexed with human IL-2, F5111.2 induced remission of type 1 diabetes in the NOD mouse model, reduced disease severity in a model of experimental autoimmune encephalomyelitis and protected mice against xenogeneic graft-versus-host disease. These results suggest that IL-2-F5111.2 may provide an immunotherapy to treat autoimmune diseases and graft-versus-host disease.

A human anti-IL-2 antibody that potentiates regulatory T cells by a structure-based mechanism