Regulation of immune function by calorie restriction and cyclophosphamide treatment in lupus-prone NZB/NZW F1 mice.
We compared the effects of calorie restriction (CR) and cyclophosphamide (CTX) on the progression of lupus nephritis and immunological changes in NZB/NZW F1 mice. Ad libitum (AL)/CTX and CR delayed onset of proteinuria and significantly decreased serum levels of anti-dsDNA, anti-histone, and circulating immune complex antibodies. CTX and CR prevented the increase in and activation of B cells, the decline in CD8(+) T cells, and maintained a higher proportion of naïve CD4(+) and CD8(+) cells. MHC class I antigen and LFA-1 expression on CD8(+) T cells and MHC class II antigen on B cells were also decreased. AL/CTX and CR prevented the increase in production of IL-10 and up-regulated IL-2 production in T cells ex vivo. We concluded that both CR and CTX can delay the onset of autoimmune disease, in part by maintaining higher numbers of naïve T cells and the immune responsiveness of T cells and decreasing the proportion of B cells.
Sun
Dongxu
D
Department of Medicine, Division of Clinical Immunology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229-3900, USA.
Krishnan
Aparna
A
Su
Jianrong
J
Lawrence
Richard
R
Zaman
Khaliquz
K
Fernandes
Gabriel
G
D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood; D000936:Antigen-Antibody Complex / Q000097:blood; D015703:Antigens, CD / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology; D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen; D016516:CD4-CD8 Ratio; D031204:Caloric Restriction; D003520:Cyclophosphamide / Q000494:pharmacology*; D004247:DNA / Q000276:immunology; D005260:Female; D006649:Histocompatibility Antigens / Q000378:metabolism; D006657:Histones / Q000276:immunology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000473:pathology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008814:Mice, Inbred NZB; D008815:Mice, Inbred Strains; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D000974:Antibodies, Antinuclear; D000936:Antigen-Antibody Complex; D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D006649:Histocompatibility Antigens; D006657:Histones; D007166:Immunosuppressive Agents; D016169:Lymphocyte Function-Associated Antigen-1; D008562:Membrane Glycoproteins; D003520:Cyclophosphamide; D004247:DNA