CD4 and secondary progressive multiple sclerosis: On the other hand, Kouchaki et al. [45] found a significantly lower frequency of CD4+CD25+FOXP3+ Tregs in MS subjects (with RRMS, PPMS, SPMS, CIS, and PRMS-progressive relapsing multiple sclerosis,) than in HCs, with the frequency of Tregs significantly higher in severe forms of MS (PPMS, SPMS, and PRMS) compared to the mild forms (CIS and RRMS) [44].