Abstract
It is known that human lymphotropic virus type I (HTLV-I) is closely associated with adult T cell leukemia (ATL). The immunological abnormality of T lymphocytes in patients with ATL is characterized by their abnormal expression of the 55 kDa chain of the receptor for interleukin 2 (IL-2 R/p55 (Tac)), and the down-regulation of CD 3 antigen. HTLV-I gene products such as p 40tax or ATL-derived factor (ADF) have been shown to enhance the expression of IL-2 R/p55 (Tac). However, the mechanism of down-regulation of CD 3 antigen on T lymphocytes in ATL patients still remains unclear. We found that CD 3 expression on peripheral blood mononuclear cells (PBMC) in healthy individuals was decreased significantly by treatment with sera and cell culture supernatants from ATL patients whose CD 3 expression on PBMC was decreased markedly, but not by sera and cell culture supernatants from ATL patients whose CD 3 expression was normal. Gel-chromatography for cell culture supernatant showed that CD 3 down-regulating activity was fractioned in the fraction number 11 which arrowed 40-60 kDa. Next, after culture with various cytokines (IL-1, IL-2, IL-4, IL-6, IFNγ and TNFα), the expression of CD 3 on normal PBMC was not reduced significantly. Furthermore, by treatment of cell culture supernatant with various anti-cytokine antibody, the expression of CD 3 antigen on normal PBMC was down-regulated. As mentioned above, there are novel factor (s) with CD 3 down-regulating activity in the sera and cell culture supernatants of those acute ATL patients. In this study, we tried to clarify the mechanism of down-regulation of CD 3 expression on ATL cells, based on the finding of soluble factor (s) down-regulating CD 3 molecule.
