IL-21 in Homeostasis of Resident Memory and Exhausted CD8 T Cells during Persistent Infection
CD4 T cells guide the development of CD8 T cells into memory by elaborating mitogenic and differentiation factors and by licensing professional antigen-presenting cells. CD4 T cells also act to stave off CD8 T cell dysfunction during repetitive antigen stimulation in persistent infection and cancer...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-09-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/21/18/6966 |
| Summary: | CD4 T cells guide the development of CD8 T cells into memory by elaborating mitogenic and differentiation factors and by licensing professional antigen-presenting cells. CD4 T cells also act to stave off CD8 T cell dysfunction during repetitive antigen stimulation in persistent infection and cancer by mitigating generation of exhausted T cells (T<sub>EX</sub>). CD4 T cell help is also required for establishing and maintaining tissue-resident memory T cells (T<sub>RM</sub>), the nonrecirculating memory T cell subset parked in nonlymphoid tissues to provide frontline defense against reinvading pathogens. Interleukin (IL)-21 is the signature cytokine secreted by follicular helper CD4 T cells (T<sub>FH</sub>) to drive B cell expansion and differentiation in germinal centers to mount high-affinity, isotype class-switched antibodies. In several infection models, IL-21 has been identified as the CD4 T help needed for formation and survival of T<sub>RM</sub> and T<sub>EX</sub>. In this review, we will explore the different memory subsets of CD8 T cells in persistent infections, the metabolic profiles associated with each, and evidence documenting the importance of CD4 T cell-derived IL-21 in regulating CD8 T<sub>RM</sub> and T<sub>EX</sub> development, homeostasis, and function. |
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| ISSN: | 1661-6596 1422-0067 |