“Inflamm‐aging” influences immune cell survival factors in human bone marrow

Abstract

The bone marrow (BM) plays a key role in the long‐term maintenance of immunological memory. However, the impact of aging on the production of survival factors for effector/memory T cells and plasma cells in the human BM has not been studied. We now show that the expression of molecules involved in the maintenance of immunological memory in the human BM changes with age. While IL‐15, which protects potentially harmful CD8+CD28− senescent T cells, increases, IL‐7 decreases. IL‐6, which may synergize with IL‐15, is also overexpressed. In contrast, a proliferation‐inducing ligand, a plasma cell survival factor, is reduced. IFN‐y, TNF, and ROS accumulate in the BM in old age. IL‐15 and IL‐6 expression are stimulated by IFN‐y and correlate with ROS levels in BM mononuclear cells. Both cytokines are reduced by incubation with the ROS scavengers N‐acetylcysteine and vitamin C. IL‐15 and IL‐6 are also overexpressed in the BM of superoxide dismutase 1 knockout mice compared to their WT counterparts. In summary, our results demonstrate the role of inflammation and oxidative stress in age‐related changes of immune cell survival factors in the BM, suggesting that antioxidants may be beneficial in counteracting immunosenescence by improving immunological memory in old age.

CD28 and CD57 define four populations with distinct phenotypic properties within human CD8+ T cells

“…Thus, although the responsiveness to IL‐7, IL‐6, and IL‐2 was quite low, DN cells may still respond well to IL‐15. The expression of IL‐15 increases in the BM in the elderly . We now observed increased levels of DN CD8 + T cells in the BM in old age, suggesting that IL‐15 may contribute to the survival of this subset.…”

Increased IL-15 Production and Accumulation of Highly Differentiated CD8+ Effector/Memory T Cells in the Bone Marrow of Persons with Cytomegalovirus

“…We demonstrated that, in the human BM, the production of IL-15 and the numbers of effector/memory CD8 + T cells increased with age and a link with inflammation was found (12, 32). However, it is still unclear how CMV positivity affects CD8 + T cells in the BM, particularly, highly differentiated effector cells.…”

Immunological memories of the bone marrow

“…In regenerating tissue of acute inflammation, this may help to get rid of tissue‐resident plasma cells of the acute immune reaction, ie, terminate the peak response. It also may contribute to the age‐dependent decay of humoral memory 49, 50…”

“…It also may contribute to the age-dependent decay of humoral memory. 49,50 Although stromal cells are a key element of the memory plasma cell niche, they are not the only element. Stromal cells do not express BAFF or APRIL themselves, and it is obvious that those ligands of BCMA, the second essential survival signal for memory plasma cells, have to be provided by other cells, which we have termed "accessory" cells of the niche.…”