Abnormalities in CD4+ T-lymphocyte subsets in inflammatory rheumatic diseases

Abstract

The monoclonal antibodies anti-2H4 and anti-4B4 identify the suppressor-inducer (CD4+2H4+) and helper-inducer (CD4+4B4+) subpopulations of CD4 (T4+) lymphocytes, respectively. The cell surface phenotype of peripheral blood lymphocytes and synovial fluid lymphocytes in patients with rheumatoid arthritis and other inflammatory joint diseases was analyzed by use of these and other well-characterized anti-T-cell monoclonal antibodies. In the synovial fluid of patients with rheumatoid arthritis, there was a markedly decreased percentage of T4+2H4+ suppressor-inducer cells (3.1 +/- 1 percent) and an increased percentage of T4+4B4+ helper-inducer cells (29.1 +/- 9 percent) as compared with the proportions found in the peripheral blood of normal individuals (T4+2H4+: 19.0 +/- 6 percent, T4+4B4+: 23.0 +/- 7 percent). Moreover, patients with other chronic and acute inflammatory joint diseases exhibited highly similar synovial T-cell findings to those of the patients with rheumatoid arthritis (T4+2H4+: 4.2 +/- 3 percent, T4+4B4+: 33.1 +/- 9 percent). In contrast, there were no significant differences between the normal control subjects and patients with rheumatoid arthritis in the percentage of T4+2H4+ cells in peripheral blood lymphocytes, nor were there significant differences between normal control subjects, patients with rheumatoid arthritis, and patients with other joint diseases (osteoarthritis, gout, B27+ spondyloarthropathy, and psoriatic arthritis) in the number of T4+4B4+ cells or in the T4/T8 ratio of peripheral blood lymphocytes. However, very low numbers of T4+2H4+ (suppressor-inducer) peripheral blood lymphocytes were seen in a subgroup of patients, including five of seven with Reiter's syndrome and several patients with systemic rheumatic disease syndromes. In addition, although the percentage of T4+2H4+ cells in peripheral blood lymphocytes of patients with osteoarthritis (13.7 +/- 7 percent) and gout (14.3 +/- 7 percent) was decreased compared with that of normal controls (19.0 +/- 6 percent) (osteoarthritis versus normal controls p <0.025), this difference appeared to reflect alterations due to age rather than disease. Consistent with the phenotypic changes observed, synovial T cells were also functionally defective, since autologous mixed lymphocyte reaction-activated T4 cells from the synovial fluid of patients with rheumatoid arthritis failed to exhibit suppressor-inducer activity. The results indicate that diminished proportions of CD4+2H4+ (suppressor-inducer) cells and increased proportions of CD4+4B4+ (helper) cells are a common feature of CD4+ cells in synovial fluid in rheumatoid arthritis as well as a variety of other inflammatory disorders, whereas modest changes in CD4+2H4+ peripheral blood lymphocytes are seen in older individuals and more marked decreases are observed only in a more selected group of patients. These changes may be of potential functional importance in the regulation of the immune response in a variety of clinical settings.