In Brief

T cells

Gfi-1 plays an important role in IL-2-mediated Th2 cell expansion. Zhu, J. et al. Proc. Natl Acad. Sci. USA 103, 18214–18219 (2006)

The transcriptional repressor growth-factor independent 1 (GFI1) has been implicated in promoting clonal expansion of T helper 2 (T_H2) cells in response to interleukin-2 (IL-2). This has now been confirmed by the generation of conditional knockout mice that lack Gfi1 in CD4⁺ T cells. CD4⁺ T cells from conditional Gfi1^−/− mice developed normally but, when placed in T_H2-cell-polarizing conditions in vitro, the clonal expansion of T_H2 cells was impaired. This defect also occurred in vivo, as fewer T_H2 cells developed in conditional Gfi1^−/− mice than in control mice after infection with Schistosoma mansoni. Consistent with a role for GFI1 in IL-2-mediated proliferation, the activation of STAT5 (signal transducer and activator of transcription 5) by IL-2 was reduced in Gfi1^−/− T cells. However, overexpression of STAT5 in Gfi1^−/− T cells did not rescue the proliferation defect, indicating that GFI1 functions downstream of, or in parallel with, STAT5 signalling to achieve optimal T_H2-cell expansion.

Immunotherapy

An essential role for Akt1 in dendritic cell function and tumor immunotherapy. Park, D. et al. Nature Biotech. 3 December 2006 (doi:10.1038/nbt1262)

Current dendritic cell (DC)-based vaccines for tumour therapy often fall short because the transfused DCs tend to be short-lived and only transiently active. So, the authors sought ways to improve DC survival and maturation, so that better T-cell responses could be induced. When DCs were deprived of GM-CSF (granulocyte/macrophage colony-stimulating factor), the amount of AKT protein declined before DC death. Exposure of the DCs to lipopolysaccharide and CD40-specific antibody restored AKT expression and prolonged DC survival. The role for AKT in supporting DC survival and maturation was confirmed by expressing a constitutively active, lipid-raft-targeted form of AKT (M_F-ΔAKT). Transfer of M_F-ΔAKT-expressing DCs into mice bearing established tumours led to robust and long-lasting tumour-specific T-cell responses that eliminated the tumours. So, enhancing DC survival by manipulating AKT might prove beneficial for future strategies of tumour immunotherapy.

Autoimmunity

Responses against islet antigens in NOD mice are prevented by tolerance to proinsulin but not IGRP. Krishnamurthy, B. et al. J. Clin. Invest. 116, 3258–3265 (2006)

Type 1 diabetes is characterized by immune responses to several autoantigens expressed by pancreatic β-cells, including proinsulin and IGRP (islet-specific glucose-6-phosphatase catalytic-subunit-related protein). But do immune responses to the individual proteins develop independently or does a response spread from one protein to another? To study this, the authors assessed the specificity of T cells arising in non-obese diabetic (NOD) mice that were made tolerant to proinsulin by overexpressing proinsulin-2 in antigen-presenting cells. These mice failed to mount T-cell responses to both proinsulin and IGRP, and this protected the mice from the development of insulitis. By contrast, mice overexpressing IGRP failed to mount responses to IGRP but still generated responses to proinsulin and developed insulitis, providing direct evidence that the immune response spreads from proinsulin to IGRP.