GITR differentially affects lung effector T cell subpopulations during influenza virus infection.
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 Ly6Chi and CX3CR1hi T cell populations represent the most differentiated effector T cells. Upon transfer, the Ly6Clo CD4+ effector T cells preferentially enter the lung parenchyma, compared to the Ly6Chi CD4+ T cells. We show that GITR had a similar effect on the accumulation of both the Ly6Chi and Ly6Clo 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 Ly6Clo CX3CR1lo subset. Moreover, GITR selectively up-regulated CXCR6 on the less differentiated CX3CR1lo CD8+ T cell subsets and induced a small but significant increase in CD127 selectively on the Ly6Clo 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.
['Chu|Kuan-Lun|KL|', 'Batista|Nathalia V|NV|', 'Girard|Mélanie|M|', 'Law|Jaclyn C|JC|', 'Watts|Tania H|TH|0000-0001-7897-4890']
D000818:Animals D000950:Antigens, Ly D015496:CD4-Positive T-Lymphocytes D018414:CD8-Positive T-Lymphocytes D000073883:CX3C Chemokine Receptor 1 D002454:Cell Differentiation D002465:Cell Movement D005260:Female D005786:Gene Expression Regulation D053450:Glucocorticoid-Induced TNFR-Related Protein D007156:Immunologic Memory D016130:Immunophenotyping D009980:Influenza A virus D053699:Interleukin-7 Receptor alpha Subunit D008168:Lung D018655:Lymphocyte Count D051379:Mice D008810:Mice, Inbred C57BL D018345:Mice, Knockout D009976:Orthomyxoviridae Infections D015398:Signal Transduction D013154:Spleen
lung influenza tissue resident memory T cells TNFR superfamily TNFRSF18