Thus, IL-2 reverses immunological tolerance in determined in vitro or in vivo circumstances, is produced at abnormally high levels in certain autoimmune diseases, and induces organ-specific autoimmune lesions when administered to patients.
In vivo-activated interleukin 2 receptor-positive T lymphocytes (Tac cells) are demonstrable and the autologous mixed leukocyte reaction (AMLR) is impaired in several autoimmune diseases, including type 1 insulin-dependent diabetes mellitus (IDDM).
The IL-2 receptor is proving to be an extraordinarily versatile therapeutic target, since it is expressed by the abnormal T cells in patients with certain lymphoid malignancies or autoimmune disorders and in individuals rejecting allografts, whereas it is not expressed by normal resting cells.
Clarifying the molecular interactions between IL-2 and its receptor complex will improve the sophistication with which these interactions are manipulated in the clinic for the treatment of autoimmune disorders and allograft rejection, treatment of lymphoid malignancies, and cytokine-based therapies for immunotherapeutic treatment of nonlymphoid cancers.
To explore the possible clinical utility of IL-2-PE664Glu for autoimmune diseases, particularly in which B cells are involved, we tested the sensitivity of B cell lines derived from myasthenia gravis patients to this chimeric cytotoxin.
T lymphocytes from several autoimmune diseases including rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) exhibit deficient mitogenic response in terms of proliferation and IL-2 production.
The abrogation of a standard T cell-dependent immune response in vivo demonstrates that IL-2-IgG-FasL can be successfully exploited to trigger the death of deleterious T cells, presenting a potentially useful strategy in the management of autoimmune diseases and allotransplant rejections.
These results suggest a rationale for combining rexinoids with IL-2R-targeted therapies in lymphoid malignancies as well as possibly in autoimmune diseases.
New forms of therapy directed at IL-2 and IL-15 receptors may be effective against certain neoplastic diseases and autoimmune disorders and in the prevention of allograft rejection.
Also, T-cell activation, as reflected in high levels of the soluble interleukin-2 receptor, appears to identify patients with DCM with a clustering of autoimmune diseases.
CONCLUSIONS Association with GD, as well as that previously reported with T1D, suggests that the CD25 region is acting as a general susceptibility locus for autoimmune disease, and is consistent with a major role for the IL-2-receptor pathway in the development and function of T cells in the control of autoimmunity.
This region harbors the interleukin 2 (IL2) and interleukin 21 (IL21) genes and was recently shown to be associated with four autoimmune diseases (Celiac disease, Type 1 diabetes, Grave's disease and Rheumatoid Arthritis).
Interleukin-2 (IL-2), one of the crucial immunoregulatory cytokines required for T lymphocyte activation, plays an important role in autoimmune diseases.
IL-2 receptor (IL2R) alpha is the specific component of the high affinity IL2R system involved in the immune response and in the control of autoimmunity.
Likewise, activation induced cell death and the induction and maintenance of regulatory T cells are the tolerance mechanisms regulated by IL-2, which convey the link between IL-2 abnormalities and the development of autoimmune disorders, such as systemic lupus erythematosus (SLE).