Quantitative restoration of immune defense in old animals determined by naive antigen‐specific CD8 T‐cell numbers

Older humans and animals often exhibit reduced immune responses to infection and vaccination, and this often directly correlates to the numbers and frequency of naive T (Tn) cells. We found such a correlation between reduced numbers of blood CD8+ Tn cells and severe clinical outcomes of West Nile virus (WNV) in both humans naturally exposed to, and mice experimentally infected with, WNV. To examine possible causality, we sought to increase the number of CD8 Tn cells by treating C57BL/6 mice with IL‐7 complexes (IL‐7C, anti‐IL‐7 mAb bound to IL‐7), shown previously to efficiently increase peripheral T‐cell numbers by homeostatic proliferation. T cells underwent robust expansion following IL‐7C administration to old mice increasing the number of total T cells (>fourfold) and NS4b:H‐2D^b‐restricted antigen‐specific CD8 T cells (twofold). This improved the numbers of NS4b‐specific CD8 T cells detected at the peak of the response against WNV, but not survival of WNV challenge. IL‐7C‐treated old animals also showed no improvement in WNV‐specific effector immunity (neutralizing antibody and in vivo T‐cell cytotoxicity). To test quantitative limits to which CD8 Tn cell restoration could improve protective immunity, we transferred graded doses of Ag‐specific precursors into old mice and showed that injection of 5400 (but not of 1800 or 600) adult naive WNV‐specific CD8 T cells significantly increased survival after WNV. These results set quantitative limits to the level of Tn reconstitution necessary to improve immune defense in older organisms and are discussed in light of targets of immune reconstitution.     

Invasion of the Zebra Mussel Dreissena polymorpha (Pallas, 1771) (Dreissenidae) in Lake Ladoga

Biology Bulletin - In May 2019, the invasive mollusk Dreissena polymorpha (Pallas, 1771) was found in Volkhov Bay of Lake Ladoga by means of an unmanned underwater vehicle. The age of some mollusks...     

The role of sex steroids and gonadectomy in the control of thymic involution

A major underlying cause for aging of the immune system is the structural and functional atrophy of the thymus, and associated decline in T cell genesis. This loss of na?ve T cells reduces adaptive immunity to new stimuli and precipitates a peripheral bias to memory cells against prior antigens. Whilst multiple mechanisms may contribute to this process, the temporal alliance of thymic decline with puberty has implicated a causative role for sex steroids. Accordingly ablation of sex steroids induces profound thymic rejuvenation. Although the thymus retains some, albeit highly limited, function in healthy adults, this is insufficient for resurrecting the T cell pool following cytoablative treatments such as chemo- and radiation-therapy and AIDS. Increased risk of opportunistic infections and cancer relapse or appearance, are a direct consequence. Temporary sex steroid ablation may thus provide a clinically effective means to regenerate the thymus and immune system in immunodeficiency states.