The effect of total lymphoid irradiation and low-dose steroids on T lymphocyte populations in multiple sclerosis: Correlation with clinical and MRI status

We have monitored the cell surface phanotypic changes occurring in T, B and NK cells of chronic progressive multiple sclerosis (MS) patients after total lymphoid irradiation (TLI) plus low-dose prednisone (TLI-LDP) therapy in comparison to sham TLI-LDP. TLI-LDP resulted in a marked reduction in the relative and absolute number of total CD3⁺ T cells, CD4⁺ helper T cells, CD4⁺CD45RA⁺ naive T cells and CD19⁺ B cells for at least 1 year after treatment. No change occurred in the percent CD8⁺ T cells although the number of these cells declined after radiotherapy. The CD4/CD8 T cell ratio was also decreased. The relative percent of CD16⁺ NK cells increased steadily after TLI-LDP while the number of NK cells transiently declined but returned to baseline values 1 year later. An increase in the percent of CD2⁺CD3^- cells and a decrease in their number after therapy was also observed. In contrast, no significant changes in the number of T, B or NK cells were seen in the MS patients receiving sham TLI-LDP. These results provide further evidence that radiotherapy causes a reduction of immunocompetent T and B cells and that a population of possibly NK cells and/or immature T cells appears to be repopulating the circulation after TLI. In addition, a correlation was observed between alterations in lymphocyte populations and the presence or absence of contrast enhancing or new T₂ lesions on brain magnetic resonance imaging (MRI) in the TLI-LDP treated MS patients. Patients devoid of contrast enhancing or new T₂ lesions had a decreased percentage of CD3₊ and CD4⁺ T cells prior to therapy and at six months following TLI-LDP compared to patients with such lesions. An association was also observed between stability in disease activity as determined on the Expanded Disability Status Scale and relative values of CD3⁺ T cells.