T cell activation niches—Optimizing T cell effector function in inflamed and infected tissues*

Abstract

Successful immunity to infection, malignancy, and tissue damage requires the coordinated recruitment of numerous immune cell subsets to target tissues. Once within the target tissue, effector T cells rely on local chemotactic cues and structural cues from the tissue matrix to navigate the tissue, interact with antigen‐presenting cells, and release effector cytokines. This highly dynamic process has been “caught on camera” in situ by intravital multiphoton imaging. Initial studies revealed a surprising randomness to the pattern of T cell migration through inflamed tissues, behavior thought to facilitate chance encounters with rare antigen‐bearing cells. Subsequent tissue‐wide visualization has uncovered a high degree of spatial preference when it comes to T cell activation. Here, we discuss the basic tenants of a successful effector T cell activation niche, taking cues from the dynamics of Tfh positioning in the lymph node germinal center. In peripheral tissues, steady‐state microanatomical organization may direct the location of “pop‐up” de novo activation niches, often observed as perivascular clusters, that support early effector T cell activation. These perivascular activation niches appear to be regulated by site‐specific chemokines that coordinate the recruitment of dendritic cells and other innate cells for local T cell activation, survival, and optimized effector function.

Albumin and interferon-β fusion protein serves as an effective vaccine adjuvant to enhance antigen-specific CD8+ T cell-mediated antitumor immunity

“…59 60 However, other IFN-modulated chemokines/cytokines couple be involved, potentially in a different manner in the tumor or LN. [61][62][63][64] Thus, further exploration on how other chemokines/cytokines may be impacted by Alb-IFNβ should be considered.…”

“…To evaluate the ability of Alb-IFNβ to promote CD8 +T cell responses to an exogenously-derived antigen, we vaccinated C57BL/6 mice with either OVA protein or E7 peptide (amino acids [43][44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62]. It has been well documented that long E7 peptide is better than short peptides at inducing robust T cell responses, and it is capable of Open access delivering specific cargo to antigen presenting cells.…”

The paradoxical role of cytokines and chemokines at the tumor microenvironment: a comprehensive review

“…The coordinated recruitment of various immune cells including effector T cells to target tissues or tumor sites accounts for successful immunity to different diseases including malignancies. Once coordinated recruitment is achieved, effector T cells leverage localized chemotactic cytokines from the tumor bed to infiltrate the tissue and interact with antigen-presenting cells to liberate effector cytokines [ 108 ]. The ability of the effector T cells to identify specific sites within cancerous tissues has been reported to be under the regulation of microanatomical display of chemotactic and adhesive signals.…”

CXCR4 controls movement and degranulation of CD8+T cells in the influenza-infected lung via differential effects on interaction and tissue scanning

“…In addition, several chemokine receptors induce T cell migration into infected tissues. For example, CXCL10 promotes CD4 + T cells to migrate into perivascular niches within the inflamed skin (Bala et al, 2022; Fowell and Kim, 2021; Gaylo-Moynihan et al, 2019; Prizant et al, 2021). Moreover, chemokines regulate T cell function during infections of the lung.…”