A biased Valpha24+ T-cell repertoire leads to circulating NKT-cell defects in a multiple sclerosis patient at the onset of his disease.

As natural killer T (NKT) cells have been implicated in the regulation of multiple sclerosis (MS), we investigated expression of the Valpha24JalphaQ canonical rearrangement in MS patients during relapses. We observed major changes in the entire blood Valpha24(+) T-cell repertoire. Seven of the eight patients showed a marked decrease in Valpha24(+) transcript number and a decrease in the diversity of the Valpha24(+) T-cell repertoire, with the exception of a few expanded clones. These perturbations, exacerbated in patient MS (A), led to circulating NKT cell defects.

The same TCR (N)Dbeta(N)Jbeta junctional region is associated with several different vbeta13 subtypes in a multiple sclerosis patient at the onset of the disease.

In multiple sclerosis (MS), the T-cell receptors (TCRS) of autoreactive T lymphocytes recognize various myelin components or derivatives including peptides of the myelin basic protein (MBP). Using the exhaustive immunoscope approach we showed that the T-cell repertoires of MS patients differ from those of healthy controls, with expansion of Vbeta13 cell clones in cerebrospinal fluid (CSF) and in peripheral blood lymphocytes (PBLs). Sequencing of the beta13(+) chains of T cells recovered from the CSF revealed high interindividual diversity, and no particular Vbeta13(+) rearrangements were shown to be myelin-autoreactive. Within the overall Vbeta13 repertoire in the CSF of patient MS3 at the onset of the disease, most of the overrepresented (N)Dbeta(N)Jbeta junctional regions were found to be associated with two or three different Vbeta13 segments. These rearrangements were most common in the PBLs of patient MS3. No such associations were detected in the Vbeta5 multigene family that was used as a control. Thus, Vbeta13 T cells infiltrating the CSF from patient MS3 may have been selected on the basis of both the Vbeta13 segments and the (N)Dbeta(N)Jbeta junctional CDR3 sequence.

[Psychological and neuropsychological problems in multiple sclerosis]. / Troubles psychiques et neuropsychologiques dans la sclérose en plaques.

Neuropsychological investigations have demonstrated that cognitive disorders are common (about 60%) in patients with multiple sclerosis. 22 patients and 22 controls participated in the study with a review of literature. The cognitive dysfunction may be termed a subcortical white matter dementia. The hallmarks are: forgetfulness, reduced speed of information processing, impaired attention and slowness of thought processes, impaired ability to manipulate acquired knowledge. Psychiatric disturbance have also high prevalence: emotional or personality changes, depression. Pathological laughing and crying are classical but not well understood. This intellectual and emotional changes in multiple sclerosis are studied by adapted psychometric psychiatric examination. Correlation of magnetic resonance imaging with neuropsychological testing is now demonstrated. Total lesion score is the best predictor of cognitive deficits, cerebral atrophy and lesions of the corpus collosium also. Neuropsychological rehabilitation techniques and symptomatic treatments must be applied to patients with multiple sclerosis.