T-cell development

The critical role of LIGHT, a TNF family member, in T cell development. Wang, J. et al. J. Immunol. 167, 5099–5105 (2001) [PubMed]

Negative selection and deletion of autoreactive thymocytes within the thymus are crucial for the maintenance of central tolerance. Here, the role of the tumour-necrosis factor family member LIGHT in these poorly defined processes is investigated. Through the generation of LIGHT transgenic mice, and by blocking the action of LIGHT in T-cell receptor transgenic mice, the authors establish that LIGHT has a crucial role in thymic negative selection.

Lymphocyte activation

Defective T cell activation and autoimmune disorder in Stra13-deficient mice. Sun, H., Lu, B., Li, R. Q., Flavell, R. A. & Taneja, R. Nature Immunol. 2, 1040–1047 (2001) [PubMed]

Taneja and colleagues describe the generation and analysis of mice deficient for the helix–loop–helix transcription factor, Stra13. At birth, and for the first few months of life, these mice were healthy, but with age a chronic lupus-like autoimmune disease developed. Several stages of CD4 T-cell activation and effector T-cell function were defective in these mice. In addition, activated T and B cells were not efficiently deleted, resulting in lymphoid organ hyperplasia and autoimmunity.

Parasite immunology

Modulation of blood fluke development in the liver by hepatic CD4+ lymphocytes. Davies, S. J. et al. Science 294, 1358–1361 (2001) [PubMed]

For some helminths, it is known that host factors can trigger alternate developmental pathways that facilitate parasite survival in adverse conditions. The trematode parasite Schistosoma mansoni has such a pathway, which is triggered by host immune deficiency. Interestingly, the absence of a previously unidentified population of CD4+ hepatic T cells is the immune signal that triggers the alternative development pathway.

Immune regulation

Membrane-bound TNF supports secondary lymphoid organ structure but is subservient to secreted TNF in driving autoimmune inflammation. Ruuls, S.R. et al. Immunity 15, 533–543 (2001) [PubMed]

Tumour-necrosis factor (TNF) is a cytokine with pleiotrophic effects in the immune system. To distinguish between the in vivo roles of secreted and membrane-bound TNF, Sedgwick and co-workers created membrane-TNF 'knock-in' mice. Membrane TNF was found to be sufficient for normal development of secondary lymphoid organs, but the inflammatory disease experimental autoimmune encephalomyelitis was less severe in these mice, indicating that secreted TNF is important in inflammatory immune responses.