Inflammation

Resolution of lung inflammation by CD44Teder, P. et al. Science 296, 155–158 (2002)

Lung injury caused by pulmonary fibrosis results in matrix deposition and inflammation. Resolution of the inflammatory response is required for the lung tissue to be repaired successfully. Teder et al. examined the role of the cell-surface adhesion molecule and hyaluronan receptor CD44 in resolving lung inflammation. Cd44−/− mice suffer from unremitting inflammation after lung injury, which is characterized by the impaired clearance of apoptotic neutrophils, the accumulation of hyaluronan fragments and the impaired activation of transforming growth factor-β1. Reconstituting these mice with CD44+ alveolar cells partially reversed the phenotype, which shows that CD44 has a role in the resolution of lung inflammation.

Immune regulation

T-bet regulates IgG class switching and pathogenic autoantibody production.Peng, S. L., Szabo, S. J. & Glimcher, L. H. Proc. Natl Acad. Sci. USA 99, 5545–5550 (2002)

T-box transcription factor T-bet has a pivotal role in the development of T-helper type 1 cells. But, what about B-cell responses? When Tbet−/− mice were crossed onto the autoimmune-prone Faslpr/lpr background, autoimmune T-cell responses remained high. However, Tbet−/−Faslpr/lpr mice did not develop antibody-mediated kidney disease or DNA-specific antibodies. Tbet−/− B cells were shown to have an impaired ability to switch to the production of IgG2a in response to interferon-γ. Preliminary studies indicate that T-bet regulates the production of germline γ2a mRNA transcripts, which are a prerequisite for isotype switching to IgG2a.

Immunotherapy

Single-chain trimers of MHC class I molecules form stable structures that potently stimulate antigen-specific T cells and B cells.Yu, Y. et al. J. Immunol. 168, 3145–3149 (2002)

The assembly of MHC-class-I–peptide complexes involves several chaperones and multiple steps, many of which are targeted by viruses to avoid immune recognition. This study reports the development of single-chain trimers (SCTs) of MHC class I molecules that eliminate the need for chaperones and might prevent these viral immune-evasion mechaisms. These peptide–spacer–β2-microglobulin–spacer–heavy-chain constructs assembled efficiently and stably at the cell surface and are recognized by cytotoxic T lymphocytes (CTLs). Unlike normal class I molecules, the expressed SCT molecules exclude competing peptides. Furthermore, SCTs are potent stimulators of peptide-specific CTLs and B cells, when delivered as a DNA vaccine, which makes them attractive as vaccine candidates.