This work reports that a subpopulation of activated CD8 T cells also produces IL-21 in the context of lymphocytic choriomeningitis virus (LCMV) infection, and identifies IL-21-expressing CD8 T cells as pivotal players in the control of chronic infection.
Abstract
CD8 T cells are critical players in immune responses against pathogens. Interleukin-21 (IL-21) is predominantly produced by CD4 T cells and exerts multifaceted effects on CD8 T cell regulation and function. Using Il21-reporter and Il21-fate mapping mice, we report that a subpopulation of activated CD8 T cells also produces IL-21 in the context of lymphocytic choriomeningitis virus (LCMV) infection. During the early effector phase of both acute and chronic infections, IL-21-expressing CD8 T cells exhibit substantial proliferative and cytotoxic capacities, with higher levels of interferon-γ (IFN-γ) and granzyme B (GZMB) compared with IL-21- counterparts. Moreover, CD8 T cell-derived IL-21 played a critical protective role in chronic, but not acute, infection. IL-21 expression in CD8 T cells appeared to be largely restricted to exhausted progenitor T cells during the exhaustion phase of chronic infection. These findings identify IL-21-expressing CD8 T cells as pivotal players in the control of chronic infection.
CD4+ cytotoxic T lymphocytes (CD4-CTLs) are understudied immune mediators with ambiguous origins. Despite expressing RUNX3, granzyme B (GZMB), and perforin (PRF1), CD4-CTLs are frequently classified as Th1 extensions due to shared interferon-γ (IFNγ) and T-BET expression. Here, we identify interleukin-27 (IL-27) as a i...
M. Matias, R. Marrocco, Kyle Magro et al.· bioRxiv· 0 citations
Interleukin-12 (IL-12) is a key immunoregulatory cytokine produced primarily by antigen-presenting cells. During infection, IL-12 orchestrates innate immune responses and shapes the nature of subsequent adaptive immunity. Specifically, by promoting interferon-γ (IFN-γ) production in helper and cytolytic T cells and nat...
Anthi Psoma, G. van den Bogaart· Immunology and Cell Biology· 0 citations
Basophils develop in the bone marrow and are associated with allergic inflammation but also contribute to protective immune responses against pathogens. Upon activation, they produce large amounts of cytokines, including interleukin (IL)-4 and IL-13. However, their physiological functions during homeostasis remain poor...
Carmen Stecher, Ines Neuwirth, Amra Begunic et al.· Frontiers in Immunology· 0 citations
Cytotoxic CD4
+
T cells (CD4
+
CTLs) have been identified as a specialized effector population characterized by potent cytotoxic machinery, including granzymes, perforin, and the Fas/FasL pathway, that enables the direct killing of MHC-II-expressing target cells. In addition to their classical helper function,...
Hao-Yang Yu, Jia-Xin Liang, Qi-Xuan Gu et al.· Cellular & Molecular Bio...· 0 citations
Chronic or persistent T cell activation is widely thought to culminate in T cell exhaustion, yet how autoreactive CD8⁺ T cells remain functionally intact despite sustained self-antigen exposure is poorly understood. In chronic infection and cancer this durability is attributed to stem-like, TCF1⁺ PD-1⁺ progenitor-exhau...
Kai-Yuan Hao, Sofia G. Baptista, Aurora Beaumond et al.· bioRxiv· 0 citations
It is shown that the absence of Notch signal causes severe CD8+ T cell exhaustion during chronic LCMV infection and demonstrated that Notch signaling is essential to promote the differentiation of Tex progenitors into Tex effector-like cells.
Dave Maurice De Sousa, Salix Boulet, F. Duval et al.· bioRxiv· 0 citations
We use cookies to run the site and, with your consent, for analytics and to show ads.
See our Cookie Policy.
