Background: Measuring proliferative responses of T lymphocytes is a simple, reproducible and widely used assay of immune competence. Evidence suggests a role of T cell reactivity in autoimmune diseases. Interferon (IFN)-β blocks in vitro proliferation of human T cells. Objectives: To assess (i) the relation between T cell proliferation and disease characteristics of MS patients, (ii) differences in T cell proliferation between subgroups and HC, and (iii) the predictive value of T cell proliferation for efficacy of IFN-β. Methods: Proliferative responses were measured in phytohaemagglutinin (PHA), anti-CD2/CD28 and anti-CD3 stimulated whole blood of 189 MS patients and 249 healthy controls (HC). Forty-eight patients started treatment with IFN-β. Based on EDSS progression, number of relapses and steroid interventions, patients were classified as either clinical responder or nonresponder to IFN-β. Results: Significant differences between MS subgroups and HC were found in T cell responses upon both PHA stimulation (RR>HC: p=0.001 and SP>HC: p=0.001) and CD2/CD28 stimulation (RR>HC, SP>HC and PP>HC: all p values <0.001). No significant differences were found between the MS subgroups. A probability of 88% (95% CI, 71-95%) for a favorable response to IFN-β was found with increased baseline proliferative T cell responses to PHA; a probability of only 16% (95% CI, 7-33%) with decreased values. Conclusion: Our results suggest that the level of T cell proliferation in whole blood predicts efficacy of IFN-β in MS.

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Journal of Neuroimmunology
Department of Neurology

Killestein, J., Hintzen, R., Uitdehaag, B., Baars, P., Roos, M., Van Lier, R. A. W., & Polman, C. H. (2002). Baseline T cell reactivity in multiple sclerosis is correlated to efficacy of interferon-β. Journal of Neuroimmunology, 133(1-2), 217–224. doi:10.1016/S0165-5728(02)00373-9