Differential responses of CD45(+ve) T-cell subsets to MBP in multiple sclerosis

The proliferative response of preparations of whole PBMC populations from 2 0 healthy individuals and 28 multiple sclerosis (MS) patients to purified p rotein derivative (PPD) and myelin basic protein (MBP) was monitored in a k inetic assay over a period of up to 10 days. PPD produced a classical secon dary response in both groups, the magnitude being significantly reduced in the MS cohort. The magnitude and pattern of response to MBP did not differ between the two populations. The kinetic profile characteristic of a primar y response was observed in both groups. Enrichment of the CD45RO(+ve) and C D45RA(+ve) T-cell subsets in PBMC led to a secondary response to PPD in the RO+ve and primary response in the RA(+ve) population in both groups. The r esponse to MBP in both RO+ve and RA(+ve) populations exhibited primary kine tics in both MS patients and healthy individuals. However, the use of T-cel l subset enriched populations allowed a finer dissection of the response to MBP which highlighted the more active role of RO-positive cells in MS pati ents. The most striking difference between patients and healthy individuals occurred on day 4 of culture when a greater response to MBP occurred in th e CD45RO enriched population, paralleling the response to PPD, in the major ity of patients. Futhermore in 4/8 patients and only1/8 healthy individuals the response in the RO+ve cultures was maintained at a higher level than t hat seen in the corresponding RA(+ve) cultures throughout the culture perio d. This data indicates that a measurable memory response to MBP exists in M S patients implying prior activation of MBP reactive T lymphocytes during t he course of disease.