Response of immunoregulatory lymphocyte subsets to methotrexate in rheumatoid arthritis

In an attempt to define the immunoregulatory mechanisms operating in rheumatoid arthritis, the authors examined peripheral blood functional lymphocyte subsets in 15 patients with active rheumatoid arthritis who were not receiving remittive therapy, as well as 33 healthy controls. The percentage and absolute numbers of total T cells (CD3), T-helper/inducer cells (CD4), and T-suppressor/cytotoxic cells (CD8) did not differ among the groups, nor did the CD4:CD8 ratio or the numbers of T cells coexpressing CD4 and the activation markers Ia or IL-2R. However, rheumatoid arthritis patients did have reduced percentages and numbers of CD4+ cells coexpressing the 2H4 antigen (CD45R-naive T cells) (P less than .0003) and CD8+ cells coexpressing the Leu-15 (CD11b) marker (suppressor/effectors) (P less than .0005). Twelve patients then received oral methotrexate, 7.5 mg weekly. Most showed clinical improvement by 4 weeks and all did by 8 weeks. Although changes in the T-cell subsets were not statistically significant, several tended toward normalization. These findings may help explain the immunoregulatory defect in rheumatoid arthritis and the effectiveness of methotrexate in modifying disease activity.