Tissue-Resident Memory T Cells in the Lungs Protect against Acute Respiratory Syncytial Virus Infection

Abstract

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection in young children. The T cell response plays a critical role in facilitating clearance of an acute RSV infection, and memory T cell responses are vital for protection against secondary RSV exposures. Tissue-resident memory (TRM) T cells have been identified as a subset of memory T cells that reside in nonlymphoid tissues and are critical for providing long-term immunity. There is currently limited information regarding the establishment and longevity of TRM T cell responses elicited following an acute RSV infection as well as their role in protection against repeated RSV infections. In this study, we examined the magnitude, phenotype, and protective capacity of TRM CD4 and CD8 T cells in the lungs of BALB/c mice following an acute RSV infection. TRM CD4 and CD8 T cells were established within the lungs and waned by 149 d following RSV infection. To determine the protective capacity of TRMs, FTY720 administration was used to prevent trafficking of peripheral memory T cells into the lungs prior to challenge of RSV-immune mice, with a recombinant influenza virus expressing either an RSV-derived CD4 or CD8 T cell epitope. We observed enhanced viral clearance in RSV-immune mice, suggesting that TRM CD8 T cells can contribute to protection against a secondary RSV infection. Given the protective capacity of TRMs, future RSV vaccine candidates should focus on the generation of these cell populations within the lung to induce effective immunity against RSV infection. ImmunoHorizons, 2021, 5: 59-69.

Tissue resident memory T cells in the respiratory tract

“…Similarly, influenza-specific CD8 + Trm in human lung tissue wane with advanced age, and this resulted in a lag in the development of an antiviral response following influenza exposure 95 . The attrition of lung CD8 + Trm is not restricted to influenza-specific Trm cells, as similar findings are observed following Sendai virus 116 , 118 and RSV 101 infections in mice. Although murine lung CD4 + CD69 + Trm also decline, their decay is less rapid relative to CD8 + Trm 18 , 51 , 119 .…”

“…Using an elegant experimental human challenge model, Jozwik et al 99 identified RSV-specific CD8 + Trm in the airways and showed that high numbers of virus specific airway CD8 + Trm, but not virus specific circulating blood T cells, correlated with less-severe lower respiratory tract symptoms and reduced viral loads post RSV challenge. Subsequent murine studies corroborate this data and show that airway and parenchyma CD8 + T cells protect against secondary RSV infection 100 , 101 .…”

The Roles of Tissue-Resident Memory T Cells in Lung Diseases

“…CD4+T RM cells and CD8+T RM cells T RM cells showed gradual differentiation with down-regulated costimulatory molecules and increased CXCR3 expression, which had been implicated in protection against RSV-induced lung pathology in mice via dendritic cells and CD8+ T cells. (43)(44)(45) Bordetella Pertussis CD69+CD4+T RM cells T RM cells produced IL-17 and IFN-g, thereby recruiting neutrophils and preventing their colonization in the nose. (46)(47)(48)(49) Influenza Viruses…”

Considerations for a Respiratory Syncytial Virus Vaccine Targeting an Elderly Population

“…Virus-specific memory T cells correlate with protection from RSV infection and are critical for reducing disease pathogenesis, making them an important population to induce through vaccination [48][49][50]. RSV-specific cellular immune responses are impaired in both their number and functional capacity in elderly adults.…”