Increased Circulating HLA‐DR⁺CD4⁺ T Cells in Systemic Lupus Erythematosus: Alterations Associated with Prednisolone Therapy

Abstract

Patients with active systemic lupus erythematosus (SLE) in the circulation have a selective increase of a subset of the CD4+ helper/inducer T cells bearing HLA-DR+, major histocompatibility complex class II antigens. We studied prednisolone-induced alterations of HLA-DR+, CD4+, and CD8+ T-cell subsets in three patients with active SLE. Prednisolone therapy was accompanied by a drastic reduction in circulating HLA-DR+, CD4+ T-cell subsets, serum anti-DNA titre, normalization of the serum immunoglobulin profile, and CD4+ T-cell responses to phytohaemagglutinin and concanavalin A. These changes in immune functions were associated with eventual improvement in the clinical condition of active SLE. A low percentage of HLA-DR+, CD8+ T-cell subsets was present in the circulation, which was not changed by prednisolone therapy. These results suggest that HLA-DR+, CD4+ T-cell subsets play a major role in the pathogenesis of active SLE, and that prednisolone-induced immunosuppression in this disease is mediated by changes in the HLA-DR+, CD4+ T-cell subsets in circulating blood.

Functional activation of lymphocyte CD44 in peripheral blood is a marker of autoimmune disease activity.

“…Alterations in circulating T cell subsets have been described in a variety of autoimmune diseases, and in many instances, this has been associated with relative increases in activated T cells (30)(31)(32)(33)(58)(59)(60)(61)(62)(63). Elevated expression of HLA-DR has been found in PBL from rheumatoid and juvenile arthritis patients as compared to normal populations (31,33,64), and increased CD25 and HLA-DR has been reported in PBL from SLE patients (30, 46).…”

Relationship between CD4+/CD8+ T Cell Ratio and T Cell Activation in Systemic Lupus Erythematosus

“…Furthermore, a decrease of CD4 z T cells with the naive phenotype (CD45RA z ) and an increase of cells with the memory phenotype (CD45RO z ) has also been reported (7)(8)(9). On the other hand, both CD4 z and CD8 z T cells are known to frequently express HLA-class II molecules (such as HLA-DR, DP) in SLE patients (10)(11)(12)(13)(14). HLA expressing T cells are thought to be in an activate phase of the cell cycle and show an anergic reaction to antigen-speci¢c and/or non-speci¢c stimuli (13,14).…”

Decreased numbers of signal-joint T cell receptor excision circle-containing CD4+ and CD8+ cells in systemic lupus erythematosus patients

“…4 Peripheral T cells of patients with SLE are abnormally activated. [13][14][15][16][17][18] Rapid division of cells is associated with increased telomerase activity. [19][20][21][22] We previously reported that the peripheral blood lymphocytes in SLE patients had a high telomerase activity, suggesting the activation of peripheral blood lymphocytes in SLE patients, resulting in rapid cell division.…”