An immunohistological study of CD4+ lymphocyte subsets within inflammatory lesions with special reference to rheumatoid arthritis and inflammatory bowel disease

Abstract

The monoclonal antibodies (mAbs) WR16, UCHL1 and WR19 identify subsets of CD4+ lymphocytes that have been functionally characterized as suppressor inducer cells or helper inducer cells. These were applied as components of a panel of lymphocyte-specific mAbs for the phenotypic analysis of lymphocyte populations within biopsies taken from rheumatoid synovial membrane and normal and inflamed gut. The phenotype of peripheral blood lymphocytes from patients with rheumatoid arthritis were also compared to normal controls. The rheumatoid synovium was characterized immunohistologically by a lymphocytic infiltrate composed predominantly of CD4+ lymphocytes and a CD4:CD8 ratio of 2.4. The CD4+ population was composed of UCHL1+ cells to the exclusion of WR16+ cells. This finding was confirmed by double immunofluorescence staining using directly conjugated Leu-3a and WR16. The UCHL1+/WR16-/CD4+ phenotype was maintained in the synovial biopsies regardless of whether the patient had commenced treatment with disease modifying drugs. The absence of WR16+ cells within the rheumatoid synovium was shown to be a localized phenomenon as there was a slight elevation of circulating WR16+ lymphocytes in the peripheral blood of rheumatoids whilst the levels of UCHL1+ and WR19+ lymphocytes remained unchanged. As no appropriate normal control tissue is available for comparison to the rheumatoid synovium we also examined the lymphocytes present within Crohn's disease-involved bowel biopsies and compared them to normal gut tissue lymphocytes using WR16 and UCHL1 mAbs. The CD3+ lymphocytes present within normal tissue comprised a mixture of WR16+ and UCHL1+ cells. In contrast the CD3+ lymphocytes within Crohn's involved tissue were exclusively UCHL1+ as previously observed in the rheumatoid synovium. These data indicate that the CD4+ lymphocyte infiltrate present within inflammatory lesions of presumed distinct aetiology exhibit a localized selective loss of cells with the CD45R+/CD4+ suppressor inducer phenotype. This may be a consequence of the selective extravasation of CD4+ helper induced cells or more likely, in view of the previously documented loss of the p220 molecule identified by CD45R mAbs upon T-cell activation, the result of CD4+ T-cell activation at sites of inflammation.