| Aplastic anemia (AA), the paradigm of bone marrow failure syndromes, is defined as pancytopenia and an empty bone marrow. The word aplastic means "unformed"; it is derived from the Greek negative prefix a and plasso, "to form". In AA, blood does not form, leading to deficiencies of granulocytes, platelets, and erythrocytes and to severe clinical consequences, of which infection and bleeding are the most important. AA is remarkable for the simplicity of its pathologic picture and the direct derivation of its clinical manifestations. Although it is not a common disease, the drama of an individual case and the larger consequences of its associations give it considerable interest.AA was first effectively treated by bone marrow transplantation to replace the absent hematopoietic stem cells. However, patients were occasionally observed to show improvement of blood counts, even after failure of donor marrow to engraft, suggesting benefit from the immunosuppressive conditioning treatment itself. With purposeful and systematic application of rabbit antilymphocyte globulin (ALG), horse antithymocyte globulin (ATG), cyclosporin A (CsA), and high doses of corticosteroids and cyclophosphamide, the great majority of patients now show sufficient improvement in hematopoiesis. Apart from the clinical evidence, laboratory data accumulated over the last three decades also have implicated an underlying immune-mediated destruction of blood forming cells as pathophysiologic, manifested in vitro by coculture inhibition of hematopoietic colony formation by the patient's T lymphocytes, an activated state of circulating cytotoxic lymphocytes, and increased production of cytokines typical of the T-helper 1 (TH1) response, especially interferon- y (IFN- γ), tumor necrosis factor a (TNF α ). Acting locally in the bone marrow, activated T cells probably induce Fas-mediated cell death of hematopoietic progenitor and stem cells, ultimately resulting in a remarked decrease in the number of these cells leading to severe pancytopenia.The immune model described above provides a powerful prism through which tofocus unanswered questions in the etiology and consequences of marrow failure. It not only helps explain the response of marrow failure to immunosuppressive treatments, but also guides laboratory investigations. To date AA is regarded as a special bone marrow failure disease which is usually mediated by abnormally activated T cells, sharing pathophysiologic mechanisms with other organ-specific autoimmune disease, like mutiple sclerosis, ulcerative colitis, uveitis, and type I diabetes.IL-15 is one of the potent T cell growth factors (TGFs), which was identified by two independent groups in 1994, based upon its ability to stimulate proliferation of the IL-2-dependent T cell line in the presence of neutralizing anti-IL-2 antibodies. It shares many molecular, biological, and immunologic features with IL-2. Both are members of the 4 a -helix bundle cytokine family, use IL-2R 3 and common chain for their action in T cells. Despite the similarities between these two cytokines, they differ dramatically in their expression levels at cellular sites and the regulation levels of synthesis and secretion. But the most important and attracting differences between them are at the functional level. IL-2, through its pivotal role in activation-induced cell death (AICD), is involved in peripheral tolerance through the elimination of selfreactive T cells. In contrast, in general IL-15 manifests antiapoptotic actions and inhibits IL-2-mediated AICD and stimulates persistence of memory phenotype CD8+T cells. So unrestricted expression of IL-15 might initiate loss of homeostasis between innate and acquired immunity, and result in serious disorders, especially autoimmune disease (AID). The relationship between IL-15 and AID has been confirmed by the studies on many AIDs, such as rheumatoid arthritis, inflammatory bowel disease, mutiple sclerosis, and sarcoidosis. It has recently been found that IL-15 appeared to exist mainly as an membrane-bou...
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