Maintenance of NF-kappaB activation in T-lymphocytes and a naive T-cell population in autoimmune-prone (NZB/NZW)F(1) mice by feeding a food-restricted diet enriched with n-3 fatty acids.
We have previously shown that feeding a fish oil (FO) supplemented diet in combination with 40% food restriction (FO/FR) has a greater impact on extending life span in lupus-prone (NZB x NZW)F1 mice than either FO ad libitum (FO/AL) or corn oil food restricted (CO/FR) alone. Lupus disease is associated with increased Th-2 (i.e., IL-6 and IL-10) cytokine production and reduced IL-2 production and NF-kappaB activation. We hypothesized that the mechanism of action by which FO/FR increases life span may involve alterations in T-lymphocyte signaling and subsequent cytokine production. To test this hypothesis, we isolated and then stimulated splenic T-lymphocytes ex vivo with anti-CD3 and -CD28 monoclonal antibodies. We report here that CO/FR and FO/FR and to a lesser extent FO/AL offset disease-associated losses in Th-1 cytokine production, CD69 expression, and NF-kappaB activation in splenic T-lymphocytes activated ex vivo. Similarly, CO/FR and FO/FR prevented the disease-dependent rise in Th-2 cytokine production ex vivo and CD69 expression in vivo. In essence, the T-lymphocyte phenotype in the old CO/FR and FO/FR groups was identical to that in the young disease-free mice. Taken together, the data suggest that both CO/FR and FO/FR increase life span, in part, by maintaining a youthful immune phenotype in autoimmune-prone mice. However, FO/FR appears to represent a more potent dietary strategy in delaying disease-associated immune dysregulation than CO/FR.
Jolly
C A
CA
Division of Clinical Immunology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas 778229-3900, USA.
Muthukumar
A
A
Reddy Avula
C P
CP
Fernandes
G
G
D000818:Animals; D017209:Apoptosis; D015551:Autoimmunity; D002478:Cells, Cultured; D004042:Dietary Fats, Unsaturated / Q000008:administration & dosage / Q000276:immunology*; D004195:Disease Models, Animal; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000276:immunology*; D005247:Feeding Behavior; D005260:Female; D007114:Immunization; D016130:Immunophenotyping; D008181:Lupus Nephritis / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D016328:NF-kappa B / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology
D004042:Dietary Fats, Unsaturated; D015525:Fatty Acids, Omega-3; D016328:NF-kappa B