The contrasting roles of IL-2 and IL-15 in the life and death of lymphocytes: implications for the immunotherapy of rheumatological diseases.
Year: 2002
Type: conference-abstract
Abstract: Intracellular communications involved in immune responses are often mediated by cytokines that show a high degree of redundancy and pleiotropy, controlling a wide range of functions in various cell types. Disordered expression of cytokines has been shown to play a role in autoimmune diseases such as rheumatoid arthritis (RA). In particular, abnormalities of TNF-α and such downstream mediators of proinflamatory activity as IL-1, IL-6, granulocyte/macrophage-colony-stimulating factor (GM-CSF), and inflammatory chemokines have been demonstrated in RA [ 1 ]. Recently, disorders involving interleukin (IL)-15 have been demonstrated in this autoimmune disease as well [ 2 – 10 ]. IL-2 and IL-15 utilize heterotrimeric receptors that include cytokine-specific private receptors IL-2Rα and IL-15Rα respectively, as well as two receptor elements, IL-2Rβ and γc, that they share [ 11 – 14 ]. We and others have shown that although IL-2 and IL-15 share two receptors and therefore share many functions, they also provide distinct and at times contrasting contributions to the life and death of lymphocytes [ 15 – 19 ]. IL-2, through its pivotal role in activation-induced cell death (AICD), is involved in peripheral tolerance through the elimination of self-reactive T cells [ 20 ]. In contrast, IL-15 in general manifests anti-apoptotic actions and inhibits AICD and stimulates the persistence of memory phenotype CD8 + T cells [ 17 , 18 ]. Abnormalities of IL-15 expression have been reported in inflammatory, autoimmune, and neoplastic diseases [ 2 – 10 , 21 – 24 ]. In particular, abnormally high levels of IL-15 transcription and translation are observed in human T-cell lymphotropic virus I (HTLV-I)-associated diseases such as the neurological disorder tropical spastic para-paresis/HTLV-I associated myelopathy (TSP/HAM) [ 23 , 24 ]. Furthermore, abnormalities of IL-15 expression have been noted in patients with autoimmune diseases such as RA and inflammatory bowel disease [ 2 – 10 , 21 – 24 ]. Therapeutic agents are being developed to target the receptor and signaling elements shared by IL-2 and IL-15 to provide effective treatment for such autoimmune disorders as well as the leukemia/lymphomas that are associated with the retrovirus HTLV-I [ 9 , 10 , 19 ].
Source: Arthritis Research
DOI: 10.1186/ar584
Author: Thomas Waldmann
Institutions: National Institutes of Health, National Cancer Institute
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: diamond
OpenAlex ID: W1546914199