The breakdown of mechanisms assuring the recognition of self and non-self is a hallmark feature of autoimmune diseases. In the past 10 years, there has been a steadily increasing interest in a subpopulation of regulatory T cells, which exert their suppressive function in vitro in a contact-dependent manner and preferentially express high levels of CD25 and forkhead and winged-helix family transcription factor forkhead box P3 (FOXP3) (TREGs). Recent findings of changed prevalences and functional efficiencies indicate that these TREGs play a unique role in autoimmune diseases. Clinical findings in patients with mutated FOXP3 genes and a specific polymorphism in the promotor region of FOXP3 also support the role of FOXP3 as a 'master control gene' in the development and functioning of TREGs. Both altered generation of TREGs and insufficient suppression of inflammation in autoimmune diseases are considered to be crucial for the initiation and perpetuation of disease. TREG-related somatic cell therapy is considered as an intriguing new intervention to approach autoimmune diseases.
Novel antigen delivery systems are currently being developed by genetic manipulation of the MHC class II trafficking pathway. Specific targeting of endogenously synthesized antigens to the class II loading compartment can result in massively enhanced presentation of peptide epitopes. This emerging technology holds promise for a variety of clinical applications including vaccine development, cancer therapies and control of autoimmune diseases.
Plasma membrane microdomains that are enriched in sphingolipids, cholesterol and glycosylphosphatidylinositol-anchored proteins appear to be important in T-cell signalling. Here, Subburaj Ilangumaran, Hai-Tao He and Daniel Hoessli discuss the possible mechanisms involved in T-cell activation via such microdomains.
The mechanisms by which gut-associated lymphoid tissue (GALT) maintains a balance between oral tolerance and active immune response in the face of exposure to high antigen concentrations remains a central question in mucosal immunity. Here, Robert Hershberg and colleagues discuss the evidence that human intestinal epithelial cells function as antigen-presenting cells (APCs) capable of regulating T-cell responses in the intestinal mucosa
The immune response to infection can vary markedly in different organs of the same animal. In some organs, the infection can resolve with subsequent immunity to re-infection, whereas in other organs, pathogens can persist. Here, Christian Engwerda and Paul Kaye highlight the importance of defining organ-specific immune mechanisms for developing strategies that deal effectively with infectious diseases and their associated pathologies.
When the immune system is under stress it can be stimulated by growth hormone. At a recent meeting*, scientists and clinicians discussed the potential for human growth hormone to act as an immunomodulator in T-cell deficiency states such as after cancer treatment, after bone marrow transplantation and during antiretroviral therapy in AIDS.
The recent report by Adkins 1 Adkins B. T-cell function in newborn mice and humans. Immunol. Today. 1999; 20: 330-335 Abstract Full Text Full Text PDF PubMed Scopus (272) Google Scholar on newborn T-cell function is timely in view of the ongoing unresolved challenge facing immunologists and vaccinologists – that of developing suitable vaccines to provide effective immunity from ‘birth till death', which is the ultimate goal of global vaccination programmes. The murine model, which determines much of what is known about human immune responses, has contributed much to our understanding of the development of fetal immune responses. However, contrary to the widely held view arising from murine studies that neonatal T-cell responses are skewed or default to a T helper 2 (Th2)-type ‘polarizing' T-cell response, we believe that a critical analysis of the published data on human neonatal T cells does not support this conclusion. Reply to Hassan and ReenBecky AdkinsImmunology TodayFebruary 01, 2000In Brief Full-Text PDF
The internet has evolved to play a central role in the lives of immunologists. Powerful search engines facilitate the location of references or suppliers at the click of a mouse. Specialized websites provide reviews for many immunological topics and links for fast navigation to related information. This article highlights websites related to monoclonal and recombinant antibodies.
In the June issue of Immunology Today, Stepp and colleagues 1. Stepp S.E. et al. Perforin: more than just an effector molecule. Immunol. Today. 2000; 21: 254-256 Abstract Full Text Full Text PDF PubMed Scopus (105) Google Scholar reviewed the growing evidence that perforin, a cytotoxic protein that lymphocytes secrete to kill virus-infected cells, also controls lymphocyte proliferation 2. Stepp S.E. et al. Perforin gene defects in familial hemophagocytic lymphohistiocytosis. Science. 1999; 286: 1957-1959 Crossref PubMed Scopus (7) Google Scholar , 3. Matloubian M. et al. A role for perforin in downregulating T-cell responses during chronic viral infection. J. Virol. 1999; 73: 2527-2536 PubMed Google Scholar , 4. Spanner D. et al. A role for perforin in activation-induced T cell death in vivo: increased expansion of allogeneic perforin-deficient T cells in SCID mice. J. Immunol. 1999; 162: 1192-1199 Google Scholar , 5. Kagi D. et al. Homeostatic regulation of CD8+ T cells by perforin. Eur. J. Immunol. 1999; 29: 3262-3272 Crossref Scopus (137) Google Scholar . This exciting idea follows from the recent findings that familial hemophagocytic lymphohistiocytosis (FHL), a fatal lymphoproliferative disorder triggered by viral infection in humans, results from a perforin defect 2. Stepp S.E. et al. Perforin gene defects in familial hemophagocytic lymphohistiocytosis. Science. 1999; 286: 1957-1959 Crossref PubMed Scopus (7) Google Scholar ; and that perforin-deficient mice exhibit a similar lymphoproliferative disorder following viral infection 3. Matloubian M. et al. A role for perforin in downregulating T-cell responses during chronic viral infection. J. Virol. 1999; 73: 2527-2536 PubMed Google Scholar . The authors suggested that perforin could trigger lymphocyte apoptosis, or repress proliferative signals, through as-yet unknown pathways. But given the evidence 2. Stepp S.E. et al. Perforin gene defects in familial hemophagocytic lymphohistiocytosis. Science. 1999; 286: 1957-1959 Crossref PubMed Scopus (7) Google Scholar , 3. Matloubian M. et al. A role for perforin in downregulating T-cell responses during chronic viral infection. J. Virol. 1999; 73: 2527-2536 PubMed Google Scholar , 4. Spanner D. et al. A role for perforin in activation-induced T cell death in vivo: increased expansion of allogeneic perforin-deficient T cells in SCID mice. J. Immunol. 1999; 162: 1192-1199 Google Scholar , 5. Kagi D. et al. Homeostatic regulation of CD8+ T cells by perforin. Eur. J. Immunol. 1999; 29: 3262-3272 Crossref Scopus (137) Google Scholar , could regulation instead be a consequence of perforin's accepted role in killing infected cells?
Apoptosis is induced in the course of immune responses to infectious agents. The last step of apoptosis is recognition and ingestion of the dying cells by phagocytes. Here, Marcela F. Lopes and colleagues discuss recent studies and argue that phagocytosis of apoptotic cells plays a previously unrecognized role in regulating the nature of immune responses against pathogens.
