Normal mouse kidneys contain activated and CD3+CD4-CD8- double-negative T lymphocytes with a distinct TCR repertoire

Healthy liver, intestine, lung, and skin harbor resident lymphocytes with conventional and unconventional phenotypes. Lymphocytes also have been detected in healthy mice kidneys; however, these cells have not been well studied and have been largely overlooked. To better characterize the intra-renal lymphocytes, we extensively perfused C57BL/6J mice with PBS and then isolated mononuclear cells for flow cytometry analysis. We observed T cells, B cells, and NK cells in normal mice kidneys after extensive perfusion. Approximately 50% of kidney T lymphocytes expressed intermediate levels of CD3 (CD3(int) T cells). Similar to liver and lung, a high percentage of unconventional CD3(+)CD4(-)CD8(-) double-negative T cells was observed in normal mice kidneys, from which 11% expressed B220 antigen. Unlike the spleen and blood, the classic CD4(+) and CD8(+) T lymphocytes in the kidney had a high proportion of activated CD69(+) and effector/memory CD44CD62L ligand phenotypes. Also, a small percentage of CD4(+)CD25(+) forkhead box p3(+) and NKT cells was observed in perfused and exanguinated kidneys. In addition, a distinct TCR repertoire was found on intra-renal conventional and unconventional T cells compared with those from the spleen. Finally, after 24 h of renal ischemia reperfusion injury (IRI), increased production of cytokines IFN-gamma and TNF-alpha by CD4(+) and CD8(+) T cells, isolated from perfused kidneys, was observed. These data suggest that some of these cells harbored in the kidney could be implicated in the immune response of the IRI pathogenic process. J. Leukoc. Biol. 84: 1400-1409; 2008.