T cells autoimmune

Lelrmann PV, Forsdiuber T, Miller A, Sercai z EE (1992) Spreading of T-cell autoimmunity to crypdc deteiminants of an autoandgen. Nature 358 155-157. 

Tian J, Lu Y, Zhang H, Chau CH, Dang HN, Kaufman DL (2004) Gamma-aminobutyric acid inliibits T cell autoimmunity and the development of inflammatory responses in a mouse type 1 diabetes model. J Immunol 173 5298—5304. 

Mutations in the FAS gene Impaired selftolerance by preventing the elimination of activated peripheral T cells Autoimmune lymphoprolifera-tive syndrome (ALPS) type la... 

Zhao M, Sun Y, Gao F, et al. Epigenetics and SEE RFXl downregulation causes CDlla and CD70 overexpression by altering epigenetic modifications in lupus CD4 + T cells. / Autoimmun. 2010 35(1) 58—69. 

Pepin et al. (1992) generated transgenic mice in which antisense RNA complementary to GR cDNA led to reduced expression mostly in neuronal tissues. Consequently, this was found to result in an impaired behavior, a defective response to stress as well as in obesity. King et al. (1995) generated transgenic mice where reduced GR expression was limited to the thymus. This leads to an altered thymocyte development, changes in the T-cell repertoire, and a reduced risk to develop autoimmune diseases. 

IFN- 3 reduces the induction by inflammatory cytokines of adhesion molecules and of MHC class I and II complex on endothelial cells, a process preceding attachment and transendothelial migration of T-cells. These anti-inflammatory effects of IFN- 3 exemplify antagonistic actions of type I and type IIIFN. There is, indeed, much clinical evidence for the involvement of IFN-y in inflammatory processes - through activation of iNOS and subsequent secretion of NO - leading to the establishment of autoimmune diseases as for instance in rheumatoid arthritis. 

On the other hand, EFN-a may also be involved in the activation of autoreactive T-cells as has been proposed for type I diabetes. An DFN-a inducible superantigen, encoded by the truncated envelope gene of a human endogenous retrovirus and specifically activating V 37 T-cells, has been detected in pancreatic lesions from type I diabetes patients, infiltrated by V 37 T-cells. Since IFN-a expression could be detected in pancreatic (3 cells in conceit with persistent viral infections, there is a clear link between viral infections and autoimmunity via IFN-a-stimulated superantigen expression. 

Bacterial or viral proteins linking T-cell receptors and MHC molecules through simultaneous interaction with the constant domains of all MHC class II molecules and of T-cell receptor (3-chains. Hence, superantigens are polyclonal T-cell activators most likely involved in the development of autoimmune diseases. 

The first mouse monoclonal antibody specific for human CD3 was produced in 1979 and named orthoclone OKT3. Aside from its use in the laboratory, OKT3 became the first anti-CD3 antibody to be utilized in transplantation medicine, but its wider application was hampered by its immunogenic and mitogenic properties (reviewed in [6]). Consequently, humanized and engineered anti-CD3 antibodies were developed to circumvent these limitations (Table 1). Since T cells and the TCR are involved in many immunological diseases, it is not surprising that the application of CD3 antibodies is not restricted to the field of transplantation. For example, CD3 antibodies are tested in clinical studies of diseases such as autoimmune diabetes (type 1 diabetes), immune-mediated inflammatory arthritis and inflammatory bowel disease [7]. 

In a mouse model for autoimmune non-obese diabetes (NOD), the full-blown diabetes could be reversed to normoglycaemia by treatment with CD3 antibodies. In these diabetes- tolerant mice, the proportions of CD4+ CD25+ regulatory T cells were increased. Moreover, the CD4+ CD25+ regulatory T cells of the tolerant mice produced high levels of... 

Lavasani S, Dzhambazov B, Andersson M (2007) Monoclonal antibody against T-cell receptor alphabeta induces self-tolerance in chronic experimental autoimmune encephalomyelitis. Scand J Immunol 65 39-47... 

HL Regulatory T cell clones induced by oral tolerance suppression of autoimmune encephalomyelitis. Science 1994 265 1237-1240. 

Singh B, Sharpe A, Bluestone JA B7/CD28 costimulation is essential for the homeostasis of the CD4-iCD25+ immunoregulatory T cells that control autoimmune diabetes. Immunity 2000 12 431-440. 

CCR5 expression likely plays a role in T-cell recruitment and may be involved in the development of autoimmune diseases. There is a negative association between the CCR5A32 mutation and rheumatoid arthritis (Prahalad 2006). Furthermore, additional studies reviewed elsewhere suggest the involvement of CCR5 in multiple sclerosis, diabetes, and transplant rejection (Ribeiro and Horuk 2005). As such, it is likely that CCR5 antagonists developed for the treatment of HIV-1 infection can also be used for other diseases. 

The role of CCR5 in the trafficking of leukocytes during CNS autoimmune diseases is poorly understood. Studies indicate that under noninflamed, physiologic states, few T cells enter the CNS and there is minimal CNS engraftment of blood-derived... 

Smith SS, Bamum SR (2008) Differential expression of beta 2-integrins and cytokine production between gammadelta and alphabeta T cells in experimental autoimmune encephalomyelitis. J Leukoc Biol 83 71-79... 

ATHERO-ELAM A montxyte adhesion molecule ATL Adult T cell leukaemia ATP Adenosine triphosphate ATPase Adenosine triphosphatase ATP-ys Adenosine 3 thiotriphosphate AITP Autoimmune thrombcKytopenic purpura AUC Area under curve AVP Arginine vasopressin... 

Over 20 infectious agents have been incriminated as etiologic agents for many the causal relationship has been disproved, and for others there is conflicting evidence. Human herpesvirus 6 (HHV-6) is currently the most likely causative virus. HHV-6 may initiate the autoimmune processes of MS in one of two ways. First, HHV-6 is structurally similar to myelin basic protein. When T cells become sensitive to HHV-6, the cells may attack myelin basic protein. Second, HHV-6 may directly stimulate the complement cascade, activating autoimmune processes.5 Infection with HHV-6 alone cannot fully explain MS, because HHV-6 is found in 75% of all people, but MS is much more rare. 

The therapeutic goal in autoimmune diseases such as RA is to control disease, to establish remission, and eventually to cure. In theory, this goal can be achieved using either Ag-specific approaches, for example, elimination of self-reactive T cells (assuming that a finite number of key Ags can be identified as the target of the autoimmune process in RA), or the non-Ag-specific approaches, for example, blockade of cytokines as in the case of TNF-a neutralization. Currently, only the latter types of approaches have yielded clinical benefit, and it is in this category that approaches to block chemokines or receptors may be included. Despite their appeal in terms of effectiveness, non-Ag-specific approaches carry a higher risk of immunosuppression and opportunistic infections (48). 

Vinuesa CG, Tangye SG, Moser B, Mackay CR. Follicular B helper T cells in antibody responses and autoimmunity. Nat Rev Immunol 2005 5(ll) 853-865. 

---