Abstract
Lupus-like renal disease in DBA/2-into-F1 (DBA --> F1) mice is driven by donor CD4 T cells and is more severe in females. Donor CD8 T cells have no known role. As expected, we observed that females receiving unfractionated DBA splenocytes (CD8 intact --> F1) exhibited greater clinical and histological severities of renal disease at 13 weeks compared to males. Surprisingly, sex-based differences in renal disease severity were lost in CD8 depleted --> F1 mice due to an improvement in females and a worsening in males. CD8 intact --> F1 female mice exhibited significantly greater donor and host effector (CD44(hi), CD62L(lo)) CD4 T cells and ICOS(hi) CD4 T follicular helper cells than males. CD8 depleted --> F1 female mice exhibited a reduction in the absolute numbers of host, but not donor CD4 Tfh cells and lost the significant increase in host CD4 effector cells vs. males. Greater female IL-21 expression, a product of Tfh cells, was seen in CD8 intact --> F1 and although reduced was still greater than male CD8 depleted --> F1 mice. Thus, donor CD8 T cells have a critical role in mediating sex-based differences in lupus renal disease severity possibly through greater host ICOS(hi) CD4 T cell involvement.
(c) 2010 Elsevier Inc. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Antibodies, Antinuclear / blood
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Antigens, CD / metabolism
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Antigens, Differentiation, T-Lymphocyte / metabolism*
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B-Lymphocytes / cytology
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B-Lymphocytes / metabolism
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Blood Urea Nitrogen
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CD4-Positive T-Lymphocytes / cytology
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CD4-Positive T-Lymphocytes / immunology*
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CD4-Positive T-Lymphocytes / metabolism
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CD4-Positive T-Lymphocytes / transplantation
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CD8-Positive T-Lymphocytes / cytology
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CD8-Positive T-Lymphocytes / immunology*
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CD8-Positive T-Lymphocytes / transplantation
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Cell Count
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Cholesterol / blood
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Female
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Gene Expression / genetics
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Gene Expression / immunology
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Glomerulonephritis, Membranous / etiology
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Glomerulonephritis, Membranous / immunology
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Glomerulonephritis, Membranous / metabolism
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Glomerulonephritis, Membranous / pathology
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Graft vs Host Disease / blood
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Graft vs Host Disease / complications
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Graft vs Host Disease / immunology*
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Graft vs Host Disease / pathology
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Immunoglobulin G / metabolism
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Inducible T-Cell Co-Stimulator Protein
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Interleukins / genetics*
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Kidney / metabolism
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Kidney / pathology
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Kidney / ultrastructure
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Lupus Nephritis / diagnosis*
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Lupus Nephritis / etiology
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Lupus Nephritis / immunology
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Lupus Nephritis / metabolism
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Lupus Nephritis / pathology
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Lymphocyte Depletion
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Male
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Mice
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Mice, Inbred DBA
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Mice, Inbred Strains
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Proteinuria / diagnosis
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Proteinuria / urine
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Serum Albumin / metabolism
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Sex Characteristics*
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Spleen / cytology
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Spleen / immunology
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Spleen / metabolism
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T-Lymphocytes / cytology
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T-Lymphocytes / immunology
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T-Lymphocytes / metabolism
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T-Lymphocytes / transplantation
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T-Lymphocytes, Helper-Inducer / cytology
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T-Lymphocytes, Helper-Inducer / metabolism
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Triglycerides / blood
Substances
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Antibodies, Antinuclear
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Antigens, CD
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Antigens, Differentiation, T-Lymphocyte
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Icos protein, mouse
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Immunoglobulin G
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Inducible T-Cell Co-Stimulator Protein
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Interleukins
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Serum Albumin
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Triglycerides
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Cholesterol
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interleukin-21