Recovery from overt type 1 diabetes ensues when immune tolerance and β-cell formation are coupled with regeneration of endothelial cells in the pancreatic islets.

Immune modulation of pancreatic inflammation induces recovery from type 1 diabetes (T1D), but remission was not durable, perhaps because of an inability to sustain the formation and function of new pancreatic β-cells. We have previously shown that Ig-GAD2, carrying GAD 206-220 peptide, induced in hyperglycemic mice immune modulation that was able to control pancreatic inflammation, stimulate β-cell regeneration, and prevent T1D progression. Herein, we show that the same Ig-GAD2 regimen given to mice with overt T1D was unable to reverse the course of disease despite eradication of Th1 and Th17 cells from the pancreas.

Mechanisms underlying antigen-specific tolerance of stable and convertible Th17 cells during suppression of autoimmune diabetes.

Type 1 diabetes involves both T helper (Th)1 and Th17 cells. While the mechanisms underlying the control of Th1 cells are relatively well defined, those operating modulation of Th17 cells remain unknown. Moreover, given that Th17 cells are plastic and can drive disease as stable or convertible T cells, effective approaches to counter type 1 diabetes would have to alter Th17 function under both circumstances.

Bone marrow-derived IL-13Rα1-positive thymic progenitors are restricted to the myeloid lineage.

The earliest thymic progenitors (ETPs) were recently shown to give rise to both lymphoid and myeloid cells. Whereas the majority of ETPs are derived from IL-7Rα-positive cells and give rise exclusively to T cells, the origin of the myeloid cells remains undefined. In this study, we show both in vitro and in vivo that IL-13Rα1(+) ETPs yield myeloid cells with no potential for maturation into T cells, whereas IL-13Rα1(-) ETPs lack myeloid potential.

Anorchia masked by septo-optic dysplasia.

Hypogonadism affecting the male pediatric population is uncommon, with that attributed to multiple unrelated etiologies being exceedingly rare. We report a case of septo-optic dysplasia, an atypical cause of delayed puberty, with subsequent workup unveiling 2 coexistent conditions: hypogonadotropic hypogonadism and anorchia. Primary and secondary etiologies must be considered in patients with undescended testes.

APCs expressing high levels of programmed death ligand 2 sustain the development of CD4 T cell memory.

The role APCs play in the transition of T cells from effector to memory remains largely undefined. This is likely due to the low frequency at which long-lived T cells arise, which hinders analysis of the events involved in memory development. In this study, we used TCR transgenic T cells to increase the frequency of long-lived T cells and developed a transfer model suitable for defining the contribution of APCs to the development of CD4 T cell memory.

FoxP3+RORgammat+ T helper intermediates display suppressive function against autoimmune diabetes.

Recently, traces of double-positive FoxP3(+)RORgammat(+) T cells were identified and viewed as dual programming differentiation intermediates geared toward development into T regulatory or Th17 cells. In this study, we report that FoxP3(+)RORgammat(+) intermediates arise in the NOD mouse T cell repertoire prior to inflammation and can be expanded with tolerogen without further differentiation. Furthermore, FoxP3(+)RORgammat(+) cells express both CD62L and membrane-bound TGFbeta and use the former to traffic to the pancreas and the latter to suppress effector T cells both in vitro and in vivo.