CD3 down‐regulating factor in sera and culture supernatants of leukaemic cells from patients with adult T cell leukaemia

Abstract

Immunological abnormality of T lymphocytes in patients with adult T cell leukemia (ATL) is characterized by abnormal expression of the 55 kD chain of the receptor for interleukin 2 (IL-2R/p55) (Tac), and the down-regulation of CD3 expression. Using serum and culture supernatants of leukaemic cells from ATL patients (Group A) whose CD3 expression was down-regulated and those (Group B) whose CD3 was not low, the possible mechanism of CD3 down-regulation on ATL cells was discussed. When PBMC from normal individuals were cultured with sera from ATL patients for 24 h, CD3 expression revealed by mean fluorescent intensity (MFI) was down-regulated by sera from ATL patients in Group 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 were cultured with supernatants of leukaemic cells from ATL patients in Group A, this CD3 down-regulating activity was also detected (MFI: Pt 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 patients in Group A decreased CD3 expression of normal PBMC significantly (MFI: Pt = 22.9 +/- 5.8, Pt 2 = 28.8 +/- 7.4, control = 92.1 +/- 9.6). This CD3 down-regulating activity in fractionated supernatant was not inhibited by any lymphokine antibodies, anti-IL-1 alpha antibody (Ab), anti-IL-1B 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. Any known cytokines (IL-1, IL-2, IL-3, IL-4, IL-6, TNF-alpha and IFN-gamma) could not modulate CD3 expression of normal PBMC. These findings suggested that there are novel factor(s) with CD3 down-regulating activity in the serum and culture supernatant of ATL patient and those factor(s) are involved in progression of ATL.

Expression and Signal Transduction of T‐Cell Antigen Receptor (TCR)/CD3 Complexes on Fresh or In Vitro Expanded T Lymphocytes from Patients with Hodgkin's and Non‐Hodgkin's Lymphomas

“…This kind of response pattern was only found in about 1/3 of the patients and to a less pronounced extent compared to normal T-cells (group III ¼ 28 patients). PBL from group I patients [21] responded very weakly to either anti-TCR/CD3 MoAb, IL-2 or the two together, and PBL from group II patients [12] had reduced responses to anti-TCR/CD3 MoAb but high responses to IL-2 (see also text to Fig. 4).…”

“…In contrast, the CD3 þ T-cells in the patients had the same amounts of TCR/CD3 complexes as normal T-cells. Thus, one defect in the T-cell population of lymphoma patients is that some CD2 þ T-cells (30-50%) have a lost or strongly decreased expression of TCR/CD3 complexes [12]. Furthermore, when T-cells from lymphoma patients were stimulated for 18 h with anti-TCR/CD3 MoAb with or without rIL-2, and the expression of early (CD69 and CD25) and late (MHC class II molecules) activation molecules analysed, a moderate decrease (30-50%) was observed in both types of patients (Fig.…”

“…The number of membrane TCR/CD3 complexes appears directly proportional to the degree of T-cell activation [11] even though few TCR/CD3 complexes seem involved in the actual triggering event(s) [50]. Dysfunction of T-cell activation has been observed in acquired or inhereted immunodeficiencies [51,52,53], in autoimmune diseases [54,55], or in certain types of cancer [12][13][14][15][16].…”

“…[16,57]) induce decreased expression of TCR/CD3 complexes [12] and/or decreased signal transduction in T-cells [13] (it has been suggested that z homodimers could be exchanged with FCRg chains (15 versus 40)). Our results do not favour any one of these explanations.…”

“…Several possible mechanisms can explain the failure to control tumour cell growth: (1) lack of recognition of tumour cell antigens; (2) induction of T-cell anergy; (3) absence of secondary stimuli necessary for T-cell activation (CD28, etc. ); (4) expression of lower numbers of TCR/CD3 complexes on the T-cell surface membrane; (5) expression of nonfunctional TCR complexes at the membrane; (6) TCR complexes are not or insufficiently connected with the intracellular protein-kinases [6][7][8][9][10][11][12][13][14][15][16]; (7) decrease or lack of expression of major histocompatibility complex (MHC) class I molecules [17].…”