Fluctuations of CD4⁺ T‐cell subsets in remitting‐relapsing multiple sclerosis

Abstract

Patients with multiple sclerosis (MS) frequently have selective depletion of the CD45R+CD4+ T-cell subset during active phases of disease. To study the relationship between changes in this subset and the onset of objective clinical exacerbations of disease, a longitudinal study was undertaken. Two CD4+ T-cell subsets and two CD8+ T-cell subsets were monitored by two-color immunofluorescence using a fluorescence-activated cell sorter. These subsets of peripheral blood lymphocytes were monitored monthly for one year in a group of 9 patients with remitting-relapsing MS and in 11 healthy age-matched control subjects. Significant changes in the ratio of two CD4+ T-cell subsets (CD45R-/CD45R+) were detected in 7 of 9 patients with MS, but not in any of the control subjects. Of those 7 persons, 4 suffered major clinical relapses substantiated by alterations in the neurological examination. The other 3 suffered minor relapses with subjective clinical abnormalities. All 7 had increased CD4+ T-cell subset ratios (%CD4+CD45R-/%CD4+CD45R+) within the month that new symptoms were reported. Most such increases resulted from a simultaneous depletion in the number of CD45R+CD4+ T cells and an increase in the number of CD45R-CD4+ T cells. One patient suffered a major relapse with no change in the ratio of CD4+ subsets but had a depletion of all CD4+ T cells. There were no consistent changes in any of the other subsets measured. These results indicate that a subgroup of patients with MS have abnormal fluctuations of two CD4+ T-cell subsets, which may correlate with increased disease activity.

Enhanced binding of lymphocytes from patients with multiple sclerosis to tumour necrosis factor-alpha (TNF-α)-treated endothelial monolayers: associations with clinical relapse and adhesion molecule expression

“…In MS, demyelination is associated with an infiltrate of predominantly CD4 + T lymphocytes, whereas CD8 + lymphocytes are prevalent in resolving lesions [2]. Onset or relapse of disease could therefore depend upon the selective recruitment into the CNS of distinct subpopulations of lymphocytes, such events being reflected by changes in their blood distribution [36] and perturbations in the expression of adhesion molecules and markers of activation [37]. We have previously suggested that disease exacerbation in MS arises from a disorder of leucocyte binding to endothelial cells at the level of the BBB [5], an interaction which is likely to be amplified by populations of lymphocytes that are predisposed to leave the circulation at sites of inflammation.…”

Suppression of Acute Experimental Allergic Encephalomyelitis by the Synthetic Sex Hormone 17-Alpha-Ethinylestradiol: An Immunological Study in the Lewis Rat

“…In an au toimmune diabetes model endogenous low numbers of CD45R+ and RT6+ cells probably reflect a maturation defect, predisposing for the development of autoimmunity [6]. In the peripheral blood of MS patients a decrease in the percentage of CD4+CD45R+ cells has been found, which correlates with disease activity [22,23]. These cells seem to lose the marker CD45R upon activation [13].…”

Fluctuations in T helper subpopulations in relapsing-remitting multiple sclerosis

“…Changes in the frequency of CD45R' and CD45R-T helper cell subsets have been previously reported in MS (10)(11)(12)(13). Rose and co-workers serially monitored these subsets in a group of 9 patients with relapsing-remitting MS and found increases in the T helper cell ratio were associated with increased disease activity (1 1).…”