Increased severity of murine lupus in female mice is due to enhanced expansion of pathogenic T cells

被引:33
作者
Lang, TJ
Nguyen, P
Papadimitriou, JC
Via, CS
机构
[1] Univ Maryland, Sch Med, Div Clin Immunol & Rheumatol, Baltimore, MD 21201 USA
[2] Univ Maryland, Sch Med, Res Serv, Baltimore Vet Affairs Med Ctr, Baltimore, MD 21201 USA
[3] Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA
关键词
D O I
10.4049/jimmunol.171.11.5795
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
A strong female predominance is a well-recognized feature of human lupus. The mechanism by which sex influences disease expression and severity is not fully understood. To address this question, we used the parent-into-F-1 (p-->F-1) model of chronic graft-vs-host disease (cGVHD) in which lupus-like humoral autoimmunity and renal disease are induced in normal F, mice. An advantage of this model is that the pathogenic T cells driving disease (donor strain) can be studied separately from nonspecifically activated T cells (host strain). We observed that lupus-like disease using female donor and host mice (f-->F cGVHD) is characterized by more severe long-term disease (glomerulonephritis) than with male donor and host (m-M cGVHD). Interestingly, differences in disease parameters could be seen at 2 wk after parental cell transfer, as evidenced by a 2- to 3-fold greater engraftment of donor CD4(+) T cells in f-->F cGVHD mice, which persisted throughout disease course. Enhanced engraftment of donor CD4(+) T cells in f-->F cGVHD mice was not due to differences in splenic homing, alloreactive precursor frequency, initial proliferation rates, or apoptotic rates, but rather to sustained high proliferation rates during wk 2 of disease compared with m-->M cGVHD mice. Crossover studies (m-->F, f-->M) demonstrated that enhanced donor CD4(+) T cell proliferation and engraftment segregate with the sex of the host. These results demonstrate that the sex of the recipient can influence the expansion of pathogenic T cells, thus increasing long-term the burden of autoreactive T cells and resulting in greater disease severity.
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页码:5795 / 5801
页数:7
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