Interaction between antigen presenting cells and autoreactive T cells derived from BXSB mice with murine lupus

Abstract

npg Systemic lupus erythematosus (SLE) is a typical autoimmune disease involving multiple systems and organs. Ample evidence suggests that autoreactive T cells play a pivotal role in the development of this autoimmune disorder. This study was undertaken to investigate the mechanisms of interaction between antigen presenting cells (APCs) and an autoreactive T cell (ATL1) clone obtained from lupus-prone BXSB mice. ATL1 cells, either before or after γ-ray irradiation, were able to activate naive B cells, as determined by B cell proliferation assays. Macrophages from BXSB mice were able to stimulate the proliferation of resting ATL1 cells at a responder/stimulator (R/S) ratio of 1/2.5. Dendritic cells (DCs) were much more powerful stimulators for ATL1 cells on a per cell basis. The T cell stimulating ability of macrophages and B cells, but not DCs, was sensitive to γ-ray irradiation. Monoclonal antibodies against mouse MHC-II and CD4 were able to block DC-mediated stimulation of ATL1 proliferation, indicating cognate recognition between ATL1 and APCs. Our data suggest that positive feedback loops involving macrophages, B cells and autoreactive T cells may play a pivotal role in keeping the momentum of autoimmune responses leading to autoimmune diseases.

Breakdown of Immune Tolerance in Systemic Lupus Erythematosus by Dendritic Cells

“…Upon activation by self-antigens, cDC can promote lupus development by interacting with T cells and B cells. While in vivo studies of how cDC affect autoreactive T cells are still lacking, in vitro evidence suggests that moDC derived from the bone marrow of lupus mice or from PBMC of SLE patients, upon activation, can promote T cell activation and hamper Treg response [ 39 , 52 , 78 – 80 ]. It is demonstrated in both mouse and human cell studies that moDC activated by apoptotic cells or cytosolic dsDNA could induce the activation of T cells, including that of autoreactive T cells [ 52 , 79 ].…”

“…It is demonstrated in both mouse and human cell studies that moDC activated by apoptotic cells or cytosolic dsDNA could induce the activation of T cells, including that of autoreactive T cells [ 52 , 79 ]. In addition, compared to bone marrow-derived macrophages, bone marrow-derived cDC (BMDC) from lupus-prone mice possessed higher ability to activate autoreactive T cells, suggesting that cDC rather than macrophages are the APC for autoreactive T cell activation [ 78 ]. Moreover, in vitro generated tolerogenic BMDC from SLE patients were less capable of generating Treg cells in vitro than HC BMDC [ 80 ].…”

Prednisone treatment inhibits the differentiation of B lymphocytes into plasma cells in MRL/MpSlac-lpr mice

“…A previous study has suggested that FasL + B cells and FasL + CD4 CD8 double negative (DN) T cells may contribute to the cytotoxic destruction of Fas + tissues in MRL/lpr mice [3] . In addition, most studies have reported that the hyper-interaction between T lymphocytes and B lymphocytes is involved [4] . Moreover, B cell hyperactivity and spontaneous antibody production have been reported in SLE.…”

Long-term follow-up after non-myeloablative transplant of bone and marrow in BXSB mice

“…[17][18][19] Aging BXSB males developed progressive monocytosis, more pronounced in the peripheral blood than in spleen. 20,21 Although monocytosis itself is inadequate to drive the disease process, 22 progression of renal pathology can be accelerated by systemic exposure of mice to lipopolysaccharide (LPS). 23 The exact role of monocytosis in BXSB remains poorly understood, and it is not clear whether it involves impairment of the functional properties of monocytes.…”