Calorie restriction modulates lymphocyte subset phenotype and increases apoptosis in MRL lpr mice

Xianghong Luan, Weiguo Zhao, Bysani Chandrasekar, Gabriel Fernandes

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

Defective expression of the Fas apoptotic gene may account for overproduction of CD4-CD8-B220+ cells (double-negative) in MRL/MpJ-lpr/lpr (lpr) mice. Previous studies have shown that calorie restriction (CR) inhibits the development of autoimmune disease and extends life span in these animals. The present studies describe the effects of CR on the distribution of lymphocyte phenotypes, lymphocyte proliferative response, and cytokine release. The effects of CR on dexamethasone (DEX)-induced apoptosis were also studied using propidium iodide (PI) uptake and DNA fragmentation in splenocytes and lymph node (LN) cells. Weanling female mice were fed a nutritionally adequate semipurified diet either ad libitum (AL) or with 40% fewer calories than AL (CR), and killed at 5 months of age. CR mice had fewer palpable lymph nodes, and decreased serum anti-dsDNA antibodies. Mitogen (ConA, anti-CD3, and LPS) and superantigen (SEB)-induced proliferative response was significantly lower in lymphoid cells from AL fed animals. FACS analysis of cells from CR animals showed decreased CD4-CD8- cells in spleen (1.7-fold, P < 0.025) and LN (1.6-fold, P < 0.01) and significantly higher CD4+ (spleen, 1.7-fold, P < 0.0001; LN, 2.6-fold, P < 0.025) and CD8+ (spleen, 1.6-fold, P < 0.001; LN, 5.2-fold, P < 0.005) cells. ConA-stimulated IL-2 release was increased in CR animals (splenocytes, 7.5-fold, P < 0.001; LN cells, 6.1-fold, P < 0.01). Finally, apoptosis in response to Dex was increased in CR animals as indicated by the presence of more PI-positive cells (spleen, 15.8%; LN, 10.7%; P < 0.01) and increased DNA fragmentation. In summary, the amelioration of autoimmune disease in MRL lpr mice by CR is accompanied by prevention of the rise in 'double-negative' T cells and by maintenance of lymphocyte responsiveness to mitogens and DEX-induced apoptosis at higher levels.

Original languageEnglish (US)
Pages (from-to)181-186
Number of pages6
JournalImmunology Letters
Volume47
Issue number3
DOIs
StatePublished - Sep 1995

Keywords

  • Apoptosis
  • Autoimmunity
  • Calorie restriction
  • Fas
  • Lupus
  • Lymphoproliferation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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