T cell transgressions: Tales of T cell form and function in diverse disease states

Abstract

Insights into T cell form, function, and dysfunction are rapidly evolving. T cells have remarkably varied effector functions including protecting the host from infection, activating cells of the innate immune system, releasing cytokines and chemokines, and heavily contributing to immunological memory. Under healthy conditions, T cells orchestrate a finely tuned attack on invading pathogens while minimizing damage to the host. The dark side of T cells is that they also exhibit autoreactivity and inflict harm to host cells, creating autoimmunity. The mechanisms of T cell autoreactivity are complex and dynamic. Emerging research is elucidating the mechanisms leading T cells to become autoreactive and how such responses cause or contribute to diverse disease states, both peripherally and within the central nervous system. This review provides foundational information on T cell development, differentiation, and functions. Key T cell subtypes, cytokines that create their effector roles, and sex differences are highlighted. Pathological T cell contributions to diverse peripheral and central disease states, arising from errors in reactivity, are highlighted, with a focus on multiple sclerosis, rheumatoid arthritis, osteoarthritis, neuropathic pain, and type 1 diabetes.

Acknowledgments

Figure 1 was adapted from "TCR downstream signaling" by BioRender (2021), retrieved from https://app.biorender.com/biorender-templates. Figure 2 was adapted from “T Cell Differentiation into Various Functional Subtypes”, by BioRender.com (2021), retrieved from https://app.biorender.com/biorender-templates. Figures 3-7 were created with BioRender.com.

Disclosure statement

The authors report no conflict of interest.

Additional information

Funding

Funding for this work was supported by NIH under Grants NS097313, DA044934, and AT009366.