- Mkhikian, Haik;
- Hayama, Ken L;
- Khachikyan, Khachik;
- Li, Carey;
- Zhou, Raymond W;
- Pawling, Judy;
- Klaus, Suzi;
- Tran, Phuong QN;
- Ly, Kim M;
- Gong, Andrew D;
- Saryan, Hayk;
- Hai, Jasper L;
- Grigoryan, David;
- Lee, Philip L;
- Newton, Barbara L;
- Raffatellu, Manuela;
- Dennis, James W;
- Demetriou, Michael
Impaired T cell immunity with aging increases mortality from infectious disease. The branching of Asparagine-linked glycans is a critical negative regulator of T cell immunity. Here we show that branching increases with age in females more than males, in naïve more than memory T cells, and in CD4+ more than CD8+ T cells. Female sex hormones and thymic output of naïve T cells (TN) decrease with age, however neither thymectomy nor ovariectomy altered branching. Interleukin-7 (IL-7) signaling was increased in old female more than male mouse TN cells, and triggered increased branching. N-acetylglucosamine, a rate-limiting metabolite for branching, increased with age in humans and synergized with IL-7 to raise branching. Reversing elevated branching rejuvenated T cell function and reduced severity of Salmonella infection in old female mice. These data suggest sex-dimorphic antagonistic pleiotropy, where IL-7 initially benefits immunity through TN maintenance but inhibits TN function by raising branching synergistically with age-dependent increases in N-acetylglucosamine.