T cells from newly diagnosed multiple sclerosis patients have enhanced responsiveness to CD46 activation

Objective

To evaluate the responsiveness of T cells from newly diagnosed multiple sclerosis (MS) patients to CD46 co-stimulation, a membrane co-factor protein potentially involved in MS pathogenesis.

Methods

T cells from MS patients and non-diseased symptomatic controls (SC) were activated in vitro with or without αCD46 antibody co-stimulation. Cytokine responses were measured to assess T-cell responsiveness. The fold difference between αCD3/CD46 and αCD3/isotype responses was calculated to determine the enhancement of CD46 activation in MS compared with SC. Additionally, the CD46 receptor phenotype, including the expression of the CD46 CYT-1 and CYT-2 isoforms, was analyzed.

Results

In the absence of αCD46 co-stimulation, MS T cells showed weaker cytokine responses compared to SC. However, CD46 engagement neutralized this deficit, resulting in a higher fold difference in MS αCD3/CD46 responses compared to SC. MS T cells also showed a trend toward a biased CD46 receptor phenotype, with a preference for the CD46 CYT-2 isoform.

Conclusions

CD46 activation enhances T-cell responses in newly diagnosed MS patients. A bias toward the CD46 CYT-2 isoform is observed, aligning with the previous findings that the absence of CYT-2 downregulation in MS might contribute to a pro-inflammatory environment.