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Reduced in vitro response of CSF lymphocytes to mitogen stimulation in multiple sclerosis
Abstract:
By means of a microculture technique and calculation of incorporation of 14C-thymidine, cerebrospinal fluid (CSF) lymphocytes from multiple sclerosis (MS) patients showed low or absent proliferation when stimulated with phytohaemagglutinin, concanavalin A, or pokeweed mitogen, in contrast to peripheral blood lymphocytes (PBL) obtained simultaneously and investigated in parallel. A lower proliferation of CSF lymphocytes compared with PBL was also found in acute aseptic meningitis, although it has been reported that CSF lymphocytes show greater proliferation than PBL when specifically stimulated. The low proliferation of MS CSF lymphocytes on mitogen stimulation may be a consequence of prolonged sensitization to an as yet unidentified antigen. The proliferation of MS CSF lymphocytes was not improved by adding irradiated PBL, making helper cell insufficiency less likely. MS CSF had no inhibitory effect on proliferation of PBL, arguing against an inhibitory effect of soluble factors in the CSF as an explanation for the depressed response of CSF lymphocytes.
Insights
Cerebrospinal fluid lymphocytes from multiple sclerosis patients exhibit significantly reduced proliferation in response to mitogens compared to peripheral blood lymphocytes. This suggests an intrinsic issue with CSF lymphocytes rather than external inhibitory factors in the cerebrospinal fluid.
Area of Science:
- Neuroimmunology
- Cellular Immunology
Background:
- Multiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous system.
- The immune response within the central nervous system, particularly involving cerebrospinal fluid (CSF) lymphocytes, is crucial in MS pathogenesis.
- Previous studies have yielded conflicting results regarding CSF lymphocyte proliferation in MS patients.
Purpose of the Study:
- To investigate the proliferative capacity of CSF lymphocytes from MS patients in response to various mitogens.
- To compare the proliferation of CSF lymphocytes with simultaneously obtained peripheral blood lymphocytes (PBL).
- To explore potential mechanisms underlying altered CSF lymphocyte function in MS.
Main Methods:
- Microculture technique utilized for lymphocyte proliferation assays.
- Quantification of 14C-thymidine incorporation to measure DNA synthesis and proliferation.
- Stimulation of lymphocytes with common mitogens: phytohaemagglutinin (PHA), concanavalin A (ConA), and pokeweed mitogen (PWM).
- Parallel assessment of CSF and PBL from the same patients, including those with acute aseptic meningitis for comparison.
Main Results:
- CSF lymphocytes from MS patients demonstrated significantly low or absent proliferation upon stimulation with PHA, ConA, and PWM.
- This reduced proliferation contrasted sharply with the robust response observed in simultaneously collected PBL.
- A similar, though less pronounced, reduction in CSF lymphocyte proliferation compared to PBL was noted in acute aseptic meningitis.
- Adding irradiated PBL did not enhance MS CSF lymphocyte proliferation, and MS CSF showed no inhibitory effect on PBL proliferation.
Conclusions:
- The findings suggest an intrinsic defect or altered functional state of CSF lymphocytes in MS patients, rather than soluble inhibitory factors within the CSF.
- Prolonged sensitization to an unknown antigen may contribute to the diminished proliferative capacity of MS CSF lymphocytes.
- Helper cell insufficiency is less likely to be the primary cause of the observed low proliferation.