T cells as a therapeutic target in SLE

Abstract

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease characterized by a loss of tolerance to multiple endogenous antigens. SLE etiology remains largely unknown, despite recent insight into the immunopathogenesis of the disease. T cells are important in the development of the disease by amplifying the immune response and contributing to organ damage. Aberrant signaling, cytokine secretion and tissue homing displayed by SLE T cells have been extensively studied and the underlying pathogenic molecular mechanisms are starting to be elucidated. T-cell targeted treatments are being explored in SLE patients. This review is an update on the T-cell abnormalities and related therapeutic options in SLE.

B Cells, Antibodies, and More

“…Patients treated for class 3 lupus nephritis attained complete remission most successfully, while those with class 5 lupus nephritis were the least likely to respond (109). It is unclear whether adjunct therapies, such as those also targeting T cells, would improve response rates because T cells can contribute to B-cell activation and mediate tissue damage in SLE (158). Favorable outcomes with rituximab treatment were associated with attaining complete B-cell depletion, reconstitution of predominantly naive and immature B cells, and sustained suppression of memory B cells and plasma cells, whereas changes in anti-dsDNA antibodies did not correlate with response (159)(160)(161).…”

Expansion of T follicular helper-T helper 1 like cells through epigenetic regulation by signal transducer and activator of transcription factors

“…It is reported that loss of the Th1/Th2 balance is related to the development of SLE 2–4. Treg cells are implicated in suppressing autoreactive effector cells and maintenance of peripheral immune tolerance 5. The role of Th17 cells in autoantibody production is contentious6 7; however, interleukin (IL)−17 was proved to promote local inflammation in the lupus kidney 8.…”

Engagement of SLAMF3 enhances CD4 + T-cell sensitivity to IL-2 and favors regulatory T-cell polarization in systemic lupus erythematosus

“…Impaired IL-2 production by activated T cells is a hallmark of both murine and human SLE (4,(11)(12)(13). Previous studies have shown that CD4 + T cells from SLE patients display lower levels of CD25, the α chain of the IL-2 receptor (IL-2R), compared with healthy subjects (14)(15)(16).…”