New Year is a time for making resolutions and reflecting on the past. But it is not always easy to refine our future actions based on analysis of our past behaviour — life is not black and white, but complex. So it is with the immune system, as illustrated by several articles in this issue. On page 55, Eddy Liew reflects on the development of the TH1/TH2 paradigm, well-known to all immunologists. But this clear-cut understanding of functional T-cell subsets and the cytokines they produce is not quite so easy to apply to real-life situations — on page 37, John O'Shea, Averil Ma and Peter Lipsky outline the complex pro-inflammatory and immunosuppressive effects of interleukin-2, the interferons, and tumour-necrosis factor in the pathogenesis of autoimmune diseases. Cytokines also feature in another article in this issue — on page 46, Leonid Gorelik and Richard Flavell describe the role of transforming growth factor-β in the regulation of T-cell homeostasis and activation.
Complexity of the immune system is also evident in the article on page 60. Although it is now clear that memory lymphocytes can exist in the absence of antigen, David Gray argues that complexity and competition in the memory-cell pool means that antigen has an important role in the maintenance of memory in vivo.
Technological advancement is an important influence on our understanding of immunology. Doreen Cantrell, on page 20, describes the importance of transgenic techniques in elucidating the signalling pathways in T cells. Alan Perelson, by contrast, outlines (on page 28) how mathematical models can be used to develop an understanding of both pathogen and lymphocyte dynamics during chronic infections, such as HIV.
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