# CD38 promotes LPS-induced innate-like activation and proliferation of CD8+ T lymphocytes in aged mice

## TL;DR

CD38 promotes inflammation and activation of CD8+ T cells in aged mice, contributing to age-related immune responses.

## Contribution

The study reveals a CD38-dependent mechanism in bystander activation of memory CD8+ T cells during aging.

## Key findings

- CD38-deficient mice showed reduced cytokine responses and fewer activated CD8+ T cells after LPS challenge.
- Wild-type aged mice had increased CD69+ TCM cells post-LPS, which was absent in CD38-deficient mice.
- CD38 promotes inflammation and bystander activation of CD8+ T cells in aged mice.

## Abstract

CD38 is a transmembrane glycoprotein involved in NAD+ metabolism, calcium signaling, and immune cell activation. Its role in the inflammatory response has been studied extensively in innate immune cells; however, its contribution to the activation of memory T lymphocytes under inflammatory conditions is less understood. Additionally, recent studies have shown an age-related increase in the expression of the protein CD38 in various human and murine tissues. Moreover, CD8+ bystander T cells have been shown to contribute to inflammation during the aging process. Given the importance of its potential role in age-related pathologies, we examined the effect of CD38 on bystander activation of CD8+ memory T cells in aged mice following lipopolysaccharide challenge. CD38-deficient mice exhibited attenuated serum cytokine responses (IL-1β, IL-6, IFN-γ, and IL-10) and a distinct CD8+ T cell profile, characterized by a decrease in activated T cells. Wild-type mice displayed a significant expansion of CD69+TCM cells after LPS inoculation, an effect that was absent in CD38-deficient animals. LPS also promoted the expression of CD69 and CD38 in TEM/EFF subsets. Thus, our findings reveal a CD38-dependent mechanism underlying bystander activation of memory CD8+ T cells in aging. Highlighting the potential contribution of CD38 to age-related diseases, such as autoimmunity, and in the face of inflammatory conditions in aged people.

Diagram illustrating the role of CD38 in bystander activation of CD8+ T cells in aged mice. Aging increases inflammation and CD38 expression, affecting immune cells. The experimental model compares aged wild-type (WT) and CD38 KO mice exposed to LPS, resulting in different CD8+T cell activation. Inflammation induces IL-6, IL-1β, and INF-γ in WT mice, promoting CD38-dependent activation. Aged KO mice show less inflammation and activation. CD38 promotes inflammation and bystander activation in aged mice.