Alterations of the expression of T-cell-related costimulatory CD28 and downregulatory CD152 (CTLA-4) molecules in patients with B-cell chronic lymphocytic leukaemia

In the present study, we have examined the kinetics and magnitude of expression of the CD28 and CD152 molecules on unstimulated and anti-CD3 + rIL-2-stimulated peripheral blood CD4+ and CD8+ T cells in patients with chronic lymphocytic leukaemia (B-CLL) and controls. The mean percentages of both CD3+ /CD4+ /CD28+ and CD3+ /CD8+ /CD28+ cells were significantly lower in B-CLL than in controls before culture, decreased rapidly, reaching their lowest levels between 24 and 48 h, and returned to basal levels after 72 h of culture. In controls, the lowest proportions of CD3+ /CD4+ /CD28+ and CD3+ /CD8+ / CD28+ cells were found after 24 h and returned to prestimulation levels after 48 h of stimulation, We observed significantly higher proportions of unstimulated CD3+ /CD4+ /CD152 + and CD3+ /CD8+ /CD152+ cells in B-CLL patients than in controls. The highest percentages of CD3+ /CD4+ /CD152 + and CD3+ /CD8+ /CD152 + cells were observed in controls after 72 h, and in B-CLL patients after 24 h, and remained statistically higher after 48, 72 and 96 h of stimulation. CD152 molecule expression returned to prestimulation levels after 96 h of culture in controls, and after 120 h in B-CLL patients. The abnormal kinetics and levels of CD28 and CD152 expression on T cells in B-CLL may lead to a state of hyporesponsiveness or anergy and could be one of the mechanisms of immune deficiency in this disease. (C) 2004 Cancer Research UK.