DOWN-REGULATION OF CD3 ANTIGEN ON ADULT T-CELL LEUKEMIA-CELLS

The immunological abnormality of T lymphocytes in patients with adult T cell leukemia (ATL) is characterized by the abnormal enhanced expres sion of the 55 kDa chain of the receptor for interleukin 2 (IL-2R/p55) (Tac), and down-regulation of CD3 antigen. Using serum and culture su pernatants of leukemic cells from ATL patients (Group A) whose CD3 exp ression was down-regulated and those whose CD3 was not low (Group B), the possible mechanism of CD3 down-regulation on ATL cells was investi gated. When PBMC from normal individuals were cultured with sera from ATL patients for 24 hrs, CD3 expression revealed by means of fluoresce nt intensity (MFI) was down-regulated by sera from ATL patients in Gro up A (MFI: Pt.1 = 51.6 +/- 4.5, Pt.2 = 48.0 +/- 6.9, Control = 96.5 +/ - 6.6), not by sera from patients in Group B (MFI: Pt.3 = 105.5 +/- 7. 9, Pt.4 = 102.5 +/- 8.3, Control = 96.5 +/- 6.6). When normal PBMC wer e cultured with supernatants of leukemic cells from ATL patients in Gr oup A, the same CD3 down-regulating activity was also detected (MFI: P t.1 = 78.0 +/- 10.2, Pt.2 = 70.6 +/- 8.7, Control = 94.0 +/- 6.6). By using gel-chromatography, the fractionated supernatants from ATL patie nts in Group A decreased CD3 expression of normal PBMC significantly ( MFI: Pt.1 = 22.9 +/- 5.8, Pt.2 = 28.8 +/- 7.4, Control = 92.1 +/- 9.6) . This CD3 down-regulating activity in fractionated supernatant was no t inhibited by any of the anti-lymphokine antibodies, anti-IL-1 alpha antibody(Ab), anti-IL-1 beta Ab, anti-IL-2 Ab, anti-IL-3 Ab, anti-IL-4 Ab, anti-IL-6 Ab, anti-TNF-alpha Ab and anti-IFN-gamma Ab. None of th e known cytokines (IL-1, IL-2, IL-3, IL4, IL-6, TNF-alpha and IFN-gamm a) modulated CD3 expression of normal PBMC. These findings suggested t hat there are novel factor(s) termed CD3 down-regulatory factor (CD3DF ) with CD3 down-regulating activity in the serum and culture supernata nt of ATL patient and those factor(s) are probably involved in the pro gression of ATL.