ORIGINAL RESEARCH article
Front. Aging
Sec. Aging and the Immune System
This article is part of the Research TopicMechanisms of T Cell Dysfunction and Immunity in AgingView all articles
CD38 promotes LPS-induced innate-like activation and proliferation of CD8+ T lymphocytes in aged mice
Provisionally accepted
Wendolaine Santiago-Cruz1
Enrique Espinosa2
Jocelyn Pérez-Lara3
Héctor Romero-Ramírez3
Priyadharshini Devarajan4
Fabio Garcia-Garcia5*
Juan Carlos Rodríguez-Alba6- 1Universidad Veracruzana, Xalapa, Mexico
- 2Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico
- 3Cinvestav Sede sur, Mexico City, Mexico
- 4Stony Brook University, Stony Brook, United States
- 5Instituto de Ciencias de la Salud, Universidad Veracruzana, Xalapa, Veracruz, Mexico
- 6Instituto Nacional de Neurologia y Neurocirugia Manuel Velasco Suarez, Mexico City, Mexico
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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.
Keywords: CD38, lipopolysaccharide, Bystander activation, CD8+ T cells, Aging, Inflammaging, T cell subsets
Received: 08 Sep 2025; Accepted: 20 Nov 2025.
Copyright: © 2025 Santiago-Cruz, Espinosa, Pérez-Lara, Romero-Ramírez, Devarajan, Garcia-Garcia and Rodríguez-Alba. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Fabio Garcia-Garcia, fgarcia@uv.mx
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