CD8⁺ Treg cells associated with decreasing disease activity after intravenous methylprednisolone pulse therapy in lupus nephritis with heavy proteinuria.
We focus on the role of CD8(+) Treg cell in Intravenous methyl-prednisolone (IVMP) pulse therapy in forty patients with active Class III/IV childhood lupus nephritis (LN) with heavy proteinuria. IVMP therapy for five days. From peripheral blood mononuclear cells (PBMCs) and renal tissues, we saw IVMP therapy definitely restoring both CD4(+)CD25(+)FoxP3(+) and CD8(+)CD25(+)Foxp3(+) Treg cell number plus greater expression with intracellular IL-10 and granzyme B in CD8(+)FoxP3(+) Treg from PBMCs. IVMP-treated CD8(+)CD25(+) Treg cells directly suppressed CD4(+) T proliferation and induced CD4(+)CD45RO(+) apoptosis. Histologically, CD4(+)FoxP3(+) as well as CD8(+)FoxP3(+) Treg cells appeared in renal tissue of LN patients before IVMP by double immunohistochemical stain. CD8(+)FoxP3(+) Treg cells increased in 10 follow-up renal biopsy specimens after IVMP. Reverse correlation of serum anti-C1q antibody and FoxP3(+) Treg cells in PBMNCs (r = -0.714, P<0.01). After IVMP, serum anti-C1q antibody decrease accompanied increase of CD4(+)FoxP3(+) Treg cells. CD8(+)Treg cells reduced interferon-r response in PBMCs to major peptide autoepitopes from nucleosomes after IVMP therapy; siRNA of FoxP3 suppressed granzyme B expression while decreasing CD8(+)CD25(+)Treg-induced CD4(+)CD45RO(+) apoptosis. Renal activity of LN by SLEDAI-2k in childhood LN was significantly higher than two weeks after IVMP (P<0.01). CD8(+)FoxP3(+) Treg cells return in post-IVMP therapy and exert crucial immune modulatory effect to control autoimmune response in LN.


BACKGROUND
DMR97-IRB-259.
Departments of Pediatrics, Changhua Christian Hospital, Changhua, Taiwan ; School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
Yi-Giien
YG
Tsai
Division of Pediatric Nephrology, China Medical University Hospital, Taichung, Taiwan.
Chia-Ying
CY
Lee
Department of Pathology, China Medical University Hospital, Taichung, Taiwan.
Tze-Yi
TY
Lin
Division of Pediatric Nephrology, China Medical University Hospital, Taichung, Taiwan ; Clinical Immunology Center, China Medical University Hospital, Taichung, Taiwan ; College of Medicine, China Medical University, Taichung, Taiwan.
Ching-Yuang
CY
Lin
D061605:Administration, Intravenous; D000293:Adolescent; D017209:Apoptosis / Q000187:drug effects; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002452:Cell Count; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology; D053804:Granzymes / Q000276:immunology; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology; D008181:Lupus Nephritis / Q000150:complications / Q000188:drug therapy* / Q000276:immunology*; D008775:Methylprednisolone / Q000008:administration & dosage / Q000627:therapeutic use*; D011507:Proteinuria / Q000150:complications / Q000188:drug therapy* / Q000276:immunology*; D020551:Pulse Therapy, Drug / Q000379:methods*; D034741:RNA, Small Interfering / Q000235:genetics / Q000494:pharmacology
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D034741:RNA, Small Interfering; D016753:Interleukin-10; D053804:Granzymes; D008775:Methylprednisolone