Characterization of kidney infiltrating T cells in the NZB/W F1 lupus model

Background

Lupus nephritis is one of the hallmarks of systemic lupus erythematosus (SLE). Although there is increasing evidence that these T lymphocytes might play a major role in the initiation and maintenance of nephritis, there is hardly any functional data about these cells.

Objective

The aim of the present study was to characterize kindey infiltrating T cells with respect to their activation state, their memory/effector phenotype, proliferation, and cytokine production. Furthermore, the ability to provide T cell help for the generation of autoantibodies was tested.

Methods

CD4⁺ T cells derived from inflamed kidney tissues of 7- to 9-month-old NZB/W F1 mice were analyzed for the expression of CD69, CD25, CD28, CD62L, CD45RB, CD44, and CD71 by FACS. Furthermore, intracellular cytokine staining was measured after PMA/Ionomycin stimulation, and the ability of kidney T cells to respond to the SmD1 83–119 peptide with increased generation of anti-dsDNA antibodies was tested by ELISPOT.

Results and Conclusion

The kidney infiltrating CD4⁺ T cells were highly activated in terms of CD69 expression (28%). The expression of CD25 was lower compared with splenic T cells (8.6% versus 15.2%). The CD4⁺ T cells were mainly of the effector/memory phenotype (55–60%), but there was also a high frequency of naïve T cells (40–45%). There was a low frequency of proliferating T cells (5%), as detected by CD71 expression. Most T cells were of the Th1 phenotype and produce proinflammatory cytokines such as IFN-γ (16.8%) and TNF-α (11.8%). Kidney T cells give no help for the generation of anti-dsDNA antibodies.