Maintenance of virgin T cells and immune functions by food restriction during aging in long-lived B6D2F₁ female mice

Animals maintained on a food-restricted (FR) dietary regimen are known to have less incidence of autoimmune disease, decreased tumor incidence, and increased life span when compared to animals on an ad libitum (AL) diet. The mechanism by which cell-mediated immunity is increased by food restriction is still unknown. The present study was undertaken in very long-lived (B6xDBA/2)F₁ female mice maintained from 16 weeks onward on an AL diet and/or 40% food restriction or both. Immunologic functions and changes in lymphocyte subsets that occur during aging were measured in 6-, 14-, and 30-month-old AL-fed and FR-fed mice. The results revealed significantly higher proliferative response of spleen cells to PHA, Con A, and staphylococcal enterotoxin B (superantigen) in 30-month-old FR animals than in AL-fed mice of the same age. Flow cytometric (FACS) analysis revealed that food restriction prevents a rise in memory T cells (Pgp-1(high)) in older mice and maintains both a higher number of virgin T cells and higher level of IL-2 production. In summary, food restriction appears to prevent the loss of anti-inflammatory cytokine-producing virgin T cell subsets during aging, increasing longevity of female mice. Further, highly increased superantigen stimulation of T cells in FR mice may be related to the presence of a higher number of virgin T cells and a decrease in memory T cells, which are known to be less responsive to bacterial superantigens.