| First Author | Chu KL | Year | 2020 |
| Journal | J Leukoc Biol | Volume | 107 |
| Issue | 6 | Pages | 953-970 |
| PubMed ID | 32125017 | Mgi Jnum | J:297744 |
| Mgi Id | MGI:6479213 | Doi | 10.1002/JLB.4AB1219-254R |
| Citation | Chu KL, et al. (2020) GITR differentially affects lung effector T cell subpopulations during influenza virus infection. J Leukoc Biol 107(6):953-970 |
| abstractText | Tissue resident memory T cells (Trm) are critical for local protection against reinfection. The accumulation of T cells in the tissues requires a post-priming signal from TNFR superfamily members, referred to as signal 4. Glucocorticoid-induced TNFR-related protein (GITR; TNFRSF18) signaling is important for this post-priming signal and for Trm formation during respiratory infection with influenza virus. As GITR signaling impacts both effector T cell accumulation and Trm formation, we asked if GITR differentially affects subsets of effector cells with different memory potential. Effector CD4(+) T cells can be subdivided into 2 populations based on expression of lymphocyte antigen 6C (Ly6C), whereas effector CD8(+) cells can be divided into 3 populations based on Ly6C and CX3CR1. The Ly6C(hi) and CX3CR1(hi) T cell populations represent the most differentiated effector T cells. Upon transfer, the Ly6C(lo) CD4(+) effector T cells preferentially enter the lung parenchyma, compared to the Ly6C(hi) CD4(+) T cells. We show that GITR had a similar effect on the accumulation of both the Ly6C(hi) and Ly6C(lo) CD4(+) T cell subsets. In contrast, whereas GITR increased the accumulation of all three CD8(+) T cell subsets defined by CX3CR1 and Ly6C expression, it had a more substantial effect on the least differentiated Ly6C(lo) CX3CR1(lo) subset. Moreover, GITR selectively up-regulated CXCR6 on the less differentiated CX3CR1(lo) CD8(+) T cell subsets and induced a small but significant increase in CD127 selectively on the Ly6C(lo) CD4(+) T cell subset. Thus, GITR contributes to accumulation of both differentiated effector cells as well as memory precursors, but with some differences between subsets. |
