Tumour Immunology

Granzymes A and B are not essential for perforin-mediated tumor rejection. Smyth, M. J. et al. J. Immunol. 171, 515–518 (2003)

The importance of perforin in tumour surveillance is clear from studies of perforin-deficient mice, which spontaneously develop B-cell lymphomas. However, what is the function of the granzyme serine proteases that are released with perforin from the cytotoxic granules of cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells? Previous studies investigating this have produced contradictory results. Using five different tumour models, Smyth and colleagues show that granzymes A and B are not essential for CTL- or NK-cell-mediated rejection of spontaneous or experimental tumours. They conclude that perforin either acts alone, or acts with another granule content, possibly an alternative granzyme, to destroy tumour cells in vivo.

Natural Killer T Cells

Cross-presentation of disialoganglioside GD3 to natural killer T cells. Wu, D. Y. et al. J. Exp. Med. 198, 173–181 (2003)

α-Galactosylceramide — a glycolipid derived from marine sponges — is a universal ligand for mouse natural killer T (NKT) cells that express a Vα14–Jα18 T-cell receptor. This ligand is presented by CD1d molecules, but no natural ligand for mouse NKT cells has been identified yet. Wu and colleagues show that mouse NKT cells can recognize the tumour-associated ganglioside GD3 in the context of CD1d molecules. Because the human melanoma cell line used to immunize the mice was CD1d negative, the authors conclude that GD3 was cross-presented to NKT cells by CD1d-positive antigen-presenting cells. This study is the first to identify a natural ligand for mouse NKT cells and also to show cross-presentation to NKT cells. Whether GD3-specific NKT cells can be induced in immunized melanoma patients is the subject of future investigation.

Technique

Cutting edge: a chemical genetic system for the analysis of kinases regulating T cell development. Denzel, A. et al. J. Immunol. 171, 519–523 (2003)

This study describes the use of ASKA (ATP analogue-sensitive kinase alleles) technology to regulate the activity of lymphocyte-specific protein tyrosine kinase (LCK) and assess its role in T-cell development. Previous attempts to assess the dose-dependent effects of LCK have required the generation of several lines of transgenic mice that express different levels of the transgene. ASKA is a chemical genetic approach that allows quantitative regulation of LCK activity rather than altering the expression levels of RNA or protein. Combining ASKA technology with reaggregate fetal thymic-organ cultures showed that there is a dose-dependent correlation between thymocyte development and LCK activity.