Disease stage-specific pathogenicity of CD138 (syndecan 1)-expressing T cells in systemic lupus erythematosus

Abstract

ObjectiveTo identify and characterize CD138 (syndecan 1)-expressing T cells in SLE-prone mice. MethodsWe characterized CD138-expressing T cells in MRL/Lpr mice by flow cytometry assay and by gene analysis. Functional properties of TCR{beta}+CD138+ cells were assessed either by activating through TCR or by co-incubating with purified B cells in the presence of auto-antigens. Purified TCR{beta}+CD138+ cells were adoptively transferred into MRL/Lpr mice and lupus disease was assessed by measuring serum auto-antibodies, proteinuria and by histopathological evaluation of kidney. ResultsWe found that the frequency of TCR{beta}+CD138+ cells was significantly higher in MRL/Lpr mice than in wild-type MRL mice (p < 0.01), and the increase in their numbers correlated with disease severity. Majority of the TCR{beta}+CD138+ cells were CD4 and CD8 double-negative and 20% were CD4. Compared to TCR{beta}+CD138- cells, TCR{beta}+CD138+ cells exhibited central memory phenotype with reduced ability to proliferate, and produce the cytokines IFN{gamma} and IL-17. When co-cultured with B cells, the ability of TCR{beta}+CD138+ cells to promote plasma cell formation and autoreactive antibody production was dependent on the presence of auto-antigens and CD4 co-receptor expression. Surprisingly, adoptively transferred TCR{beta}+CD138+ cells slowed down the disease progression in young MRL/Lpr mice but had the opposite effect when DNA was co-administered or when TCR{beta}+CD138+ cells were transferred into older MRL/Lpr mice with established disease. ConclusionHere, we provided evidence for the pathogenic role of CD138-expressing T cells when auto-antigens are exposed to immune system. Thus, monitoring the changes in TCR{beta}+CD138+ cell-frequency may serve as a tool to assess SLE severity. Moreover, CD138-expressing T cells may be targeted to alleviate lupus progression.