CD4 subsets (CD45RA/RO) exhibit differences in proliferative responses, IL-2 and gamma-interferon production during intravenous methylprednisolone treatment of multiple sclerosis

Abstract

Phytohaemagglutinin (PHA)-induced proliferative responses, interleukin 2 (IL-2) and gamma-interferon production were determined in purified CD4CD45RA and CD4CD45RO lymphocytes isolated by immunomagnetic bead separations from normal subjects and multiple sclerosis (MS) patients. Significantly higher proliferative activities were observed for CD4CD45RA cells compared with the corresponding CD4CD45RO cell population in normal subjects and MS patients. CD4CD45RA lymphocyte proliferative responses declined by 50% 3 h following a single dose (500 mg) of intravenous methylprednisolone (IVMP). At 24 h, levels were similar to those determined pre-therapy, as were the levels observed 24 h after a 5-day course (500 mg daily) of IVMP. In contrast, CD4CD45RO cells were unaffected by IVMP. In vitro incorporation of methylprednisolone (10(-6) M) to cell cultures resulted in a modest reduction in proliferative activities of both CD4 subsets. In MS patients subnormal levels of IL-2 and gamma-interferon were observed in PHA-stimulated cultures of CD4CD45RA and CD4CD45RO cells. Following 5 days of IVMP therapy, IL-2 and gamma-interferon production was similar to that observed in CD4CD45RA and CD4CD45RO cells from normal subjects. IVMP therapy causes selective, but transient, inhibition of CD4CD45RA lymphocyte proliferative responses and enhancement of PHA-induced IL-2 and gamma-interferon production by both CD4CD45RA and CD4CD45RO cells.