Cell number requirements for lymphocyte stimulation in vitro: changes during the course of multiple sclerosis and the...

Peripheral blood lymphocytes from 20 patients with clinically definite, relapsing and remitting multiple sclerosis (MS) were studied during their participation in a double-blind trial of immunosuppressive treatment. Proliferative responses occurring with different numbers of cells in culture and on different days of culture in the presence of phytohaemagglutinin (PHA) or with allogeneic cells from lymphoid cell lines (MLC) were assessed. Cells taken from patients before treatment showed similar responses to cells from laboratory personnel. However, when cells were taken from patients in relapse or from untreated patients as the disease progressed, there was an alteration in the pattern of response; higher number of cells were required in culture to produce responses. A change in the responsiveness to PHA or in MLC may therefore accompany the progression of the disease in MS (reflecting clinical relapses and possibly subclinical activity of the disease), perhaps resulting from a simple reduction in the proportion of cells able to respond. After intense immunosuppression followed by long-term maintenance on azathioprine, cells from patients gave similar responses to those found before treatment. Thus long-term immunosuppression prevented the progressive alteration in lymphocyte function. Shifts in the total cell number and time in culture required to allow proliferation with mitogens of cells from untreated MS patients could explain both the 'low' of PHA responses reported and the changes of in vitro 'suppressor' function of these cells.