Natural killer cells

Cytolytic granule polarization and degranulation controlled by different receptors in resting NK cells. Bryceson, Y. T. et al. J. Exp. Med. 202, 1001–1012 (2005)

Bryceson et al. developed a system using Drosophila melanogaster Schneider cell 2 (SC2) cells transfected with individual ligands for natural killer (NK)-cell activating receptors to investigate the role of the receptors in target-cell lysis mediated by resting human NK cells. Expression of the lymphocyte function-associated antigen 1 (LFA1) ligand intercellular adhesion molecule 1 (ICAM1) by SC2 cells induced polarization of NK-cell granules, but it did not induce degranulation or cytotoxicity. By contrast, ligation of CD16 at the surface of NK cells (through expression of IgG by the SC2 cells) induced degranulation, but not polarization of NK-cell granules or target-cell lysis. Resting human NK cells did mediate target-cell lysis when both LFA1 and CD16 were engaged, indicating that granule polarization and degranulation are uncoupled in these cells.

Antibodies

Engineering the Fc region of immunoglobulin G to modulate in vivo antibody levels. Vaccaro, C. et al. Nature Biotechnol. 23, 1283–1288 (2005)

The authors of this paper took a novel approach to antibody engineering and generated a human IgG1 variant with a mutated Fc region. The mutant was designed to reduce endogenous levels of IgG by exploiting the activity of the Fc receptor FcRn, which regulates IgG concentrations. The mutant IgG1 bound FcRn with higher affinity and with less pH dependence than did wild-type IgG. Because binding to FcRn protects IgG molecules from degradation and, instead, recycles them, preferential binding to FcRn by the mutant IgG1 resulted in increased degradation of endogenous IgG1. The authors propose that this could be a useful reagent for clearing pathogenic autoantibodies in autoimmune diseases such as systemic lupus erythematosus.

Tumour immunology

Tumor-associated CD8+ T cell tolerance induced by bone marrow-derived immature myeloid cells. Kusmartsev, S. et al. J. Immunol. 175, 4583–4592 (2005)

This study shows that the immature myeloid cells (iMCs) that accumulate in large numbers in the spleen, lymph nodes and tumour tissues of tumour-bearing mice can take up and present tumour antigens to CD8+ T cells in vivo to induce antigen-specific tolerance. In a model of adoptive transfer of transgenic T cells to tumour-free mice, the addition of iMCs isolated from tumour-bearing mice inhibited the T-cell response to specific antigen in an MHC-class-I-dependent manner. Furthermore, iMCs from mice that were injected with ovalbumin (OVA)-expressing tumour cells displayed an OVA-derived epitope on their surface and inhibited OVA-specific T-cell responses. T-cell tolerance is an important mechanism of tumour escape, and in this model, the number of iMCs correlated directly with the size of the tumour. Therefore, targeting iMCs could be a useful strategy to improve the efficacy of cancer vaccines.