Blockade of CD28/CTLA4 pathway prevented almost diseases and lymphadenopathy but not lung disease in MRL/lpr mice

We studied role of CD28/CTLA4 costimulatory T cell activation pathway on the pathogenesis of MRL/lpr mice. Administration of CTLA4IgG inhibited not only autoantibody production and end-organ diseases in kidney, salivary gland and liver but lymphadenopathy, however, lung disease was not inhibited Additional analysis demonstrated that after CTLA4IgG treatment (i) activation of and IL-4 production from conventional T cells, (ii) IFNg production from CD4-CD8-B220+ T cells, and (iii) differentiation from activated B lymphocytes to plasma cells were prevented but (iv) development of CD4-CD8-B220+ T cells and (v) activation of B lymphocytes and macrophage containing fraction was still induced. Thus, we concluded that in MRL/lpr mice CD28/CTLA4 pathway mediated (i) differentiation of conventional T cells to Th2/Tc2-like cells, (ii) differentiation of B cells to plasma cells, (iii) IFNg production from CD4-CD8-B220+ T cells and (iv) accumulation of lymphoid cell populations however, (v) development of CD4-CD8-B220+ T cells and (vi) activation of B lymphocytes and macrophages were not mediated by CD28/CTLA4 pathway.