Background and aim: Multiple sclerosis is a demyelinating disease that leads to progressive neurodegeneration. It is the result of abnormal immune system activation, allowing self-targeting CD4+ immune cells to enter the central nervous system and initiate inflammation. This process triggers antibody production and the release of pro-inflammatory cytokines, resulting in eventual myelin sheath damage. The objective of this study was to examine T regulatory cells (Tregs) and monocytes, specifically focusing on the expression of CTLA-4 (CD152) and FOXP3+ in CD4+CD25+ Tregs, as well as the expression of CD40+ and CD192+ in monocyte subpopulations among individuals with primary progressive multiple sclerosis (PPMS). Additionally, we measured serum neurofilament light (sNfL) concentrations in both PPMS subjects and a control group. Subject and methods: The immunological analysis was performed on peripheral blood samples obtained from 28 PPMS participants (15 receiving ocrelizumab treatment and 13 untreated) and 10 healthy control subjects (HCs). Blood samples were treated with anti-human CD4, CD25, FOXP3, and CTLA-4 antibodies for lymphocyte analysis and anti-human CD14, CD16, CD40, and CD192 antibodies for monocyte analysis. Serum samples were utilized in an ELISA test to determine sNfL concentrations. Results: The findings indicate that both ocrelizumab-treated (N=15) and untreated (N=13) PPMS subjects exhibited a significantly higher percentage of CTLA-4+ and FOXP3+ in CD4+CD25+ Tregs compared to HCs. Furthermore, ocrelizumab-treated PPMS subjects showed a significantly lower percentage of CD192+ and CD40+ in non-classical monocytes when compared to untreated subjects. No significant differences in sNfL concentrations were observed among treated PPMS, untreated PPMS, and HCs. Conclusion: The elevated percentages of CTLA-4+ and FOXP3+ in CD4+CD25+ Tregs among both treated and untreated PPMS subjects suggest a suppressive role of Tregs in modulating the aberrant immune response associated with PPMS. The reduced percentages of CD40+ and CD192+ in CD14+CD16++ monocytes in treated subjects compared to untreated ones may indicate the potential role of ocrelizumab in suppressing central nervous system inflammation.