TY - JOUR
T1 - Renal ischemia-reperfusion leads to long term infiltration of activated and effector-memory T lymphocytes
AU - Ascon, Miguel
AU - Ascon, Dolores B.
AU - Liu, Manchang
AU - Cheadle, Chris
AU - Sarkar, Chaitali
AU - Racusen, Lorraine
AU - Hassoun, Heitham T.
AU - Rabb, Hamid
N1 - Funding Information:
This study was supported by NIH Grants: 3R01DK054770-06A1 (MA), 3R01DK054770-05S1 (DBA), R01 DK54770, and SCCOR HL073944 (HR). We thank Hye Ryoun Jang for flow cytometry assistance during the depletion studies.
PY - 2009/3
Y1 - 2009/3
N2 - It is well-established that significant ischemia-reperfusion injury during kidney transplantation results in increased incidence of long-term fibrosis and rejection. To test for a role of T cell infiltration and activation following ischemic injury, we induced both bilateral and unilateral renal ischemia in mice, followed by reperfusion, and then isolated mononuclear cells. Analysis of these cells by flow cytometry showed that 2 weeks after bilateral ischemia there was a significant increase of CD8+ T cells. Furthermore, both CD4+ and CD8+ T cells infiltrated the injured kidney 6 weeks after unilateral ischemia. These T cells had increased expression of CD69+ and CD44hiCD62L-, markers of activation and effector-memory, respectively. CD4+NK1.1+ and CD19+ B cells were decreased in percentage both 6 and 11 weeks after bilateral or unilateral injury. There was a significant upregulation of IL-1Β, IL-6, TNF-α, IFN-γ, MIP-2, and RANTES expression, measured by real-time PCR, 6 weeks after unilateral renal ischemia, further indicating T cell activation. Depletion of CD4+ and CD8+ T cells before ischemia caused less medullary damage and reduced kidney IFN-γ expression, whereas their depletion following ischemia increased kidney IL-1Β; however, depletion of these cells had no effect on histological damage to the kidney. Our study demonstrates that moderate or severe kidney ischemia induces long-term T lymphocyte infiltration and cytokine/chemokine upregulation, leading to kidney structural changes.
AB - It is well-established that significant ischemia-reperfusion injury during kidney transplantation results in increased incidence of long-term fibrosis and rejection. To test for a role of T cell infiltration and activation following ischemic injury, we induced both bilateral and unilateral renal ischemia in mice, followed by reperfusion, and then isolated mononuclear cells. Analysis of these cells by flow cytometry showed that 2 weeks after bilateral ischemia there was a significant increase of CD8+ T cells. Furthermore, both CD4+ and CD8+ T cells infiltrated the injured kidney 6 weeks after unilateral ischemia. These T cells had increased expression of CD69+ and CD44hiCD62L-, markers of activation and effector-memory, respectively. CD4+NK1.1+ and CD19+ B cells were decreased in percentage both 6 and 11 weeks after bilateral or unilateral injury. There was a significant upregulation of IL-1Β, IL-6, TNF-α, IFN-γ, MIP-2, and RANTES expression, measured by real-time PCR, 6 weeks after unilateral renal ischemia, further indicating T cell activation. Depletion of CD4+ and CD8+ T cells before ischemia caused less medullary damage and reduced kidney IFN-γ expression, whereas their depletion following ischemia increased kidney IL-1Β; however, depletion of these cells had no effect on histological damage to the kidney. Our study demonstrates that moderate or severe kidney ischemia induces long-term T lymphocyte infiltration and cytokine/chemokine upregulation, leading to kidney structural changes.
KW - Cell depletion
KW - Long-term infiltration
KW - Renal ischemia
KW - T lymphocytes
UR - http://www.scopus.com/inward/record.url?scp=60749095669&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=60749095669&partnerID=8YFLogxK
U2 - 10.1038/ki.2008.602
DO - 10.1038/ki.2008.602
M3 - Article
C2 - 19092796
AN - SCOPUS:60749095669
SN - 0085-2538
VL - 75
SP - 526
EP - 535
JO - Kidney international
JF - Kidney international
IS - 5
ER -