Airway T cells protect against RSV infection in the absence of antibody

Abstract

Tissue resident memory T cells (Trm) act as sentinels and early responders to infection. RSV specific Trm have been detected in the lungs after human RSV infection, but whether they play a protective role is unknown. To dissect the protective function of Trm, BALB/c mice were infected with RSV; infected mice developed antigen specific CD8 + Trm (CD103 + /CD69 + ) in the lungs and airways.Intranasally transferring cells from the airways of previously infected animals to naïve animals reduced weight loss on infection in the recipient mice. Transfer of airway CD8 cells led to reduced disease and viral load and increased IFNγ in the airways of recipient mice, whilst CD4 transfer reduced TNFα in the airways. Because DNA vaccines induce a systemic T cell response, we compared vaccination with infection for the effect of memory CD8 cells generated in different compartments. Intramuscular DNA immunization induced RSV specific CD8 T cells, but they were immunopathogenic not protective. Notably, there was a marked difference in the induction of Trm; infection but not immunization induced antigen specific Trm in a range of tissues. These findings demonstrate a protective role for airway CD8 against RSV and support the need for vaccines to induce antigen specific airway cells.3

Cytokines and CD8 T cell immunity during respiratory syncytial virus infection

“…As described in other infection models, RSV infection induces the generation of antigenspecific T RM expressing CD69 and CD103 within the lung parenchyma ( Fig. 1c) [38,56]. Additionally, RSV-specific T RM within the lung can also be generated by local immunization with RSV-derived antigens [12,57,58].…”

“…Recent studies have demonstrated that T RM play a critical role in providing protection against secondary influenza virus infections [66][67][68]. Importantly, several reports have also supported a role for RSV-specific T RM in providing protection against RSV infection [12,[56][57][58]. Together, these studies establish that memory CD8 T cells provide protection against secondary RSV infection.…”

“…Mice previously infected with RSV exhibit significantly enhanced control of LM in the spleen compared to naive mice, suggesting a protective role of memory CD8 T cells. Alternatively, the transfer of sorted airway memory CD8 T cells significantly reduces lung RSV RNA levels following RSV challenge compared to mice receiving either no cells or sorted CD4 T cells [56]. Other studies have used peptide epitope vaccinations to generate pre-existing, systemic RSV-specific memory CD8 T cells that significantly accelerated viral clearance following RSV challenge [11,12].…”

Tissue‐resident innate immunity in the lung

“…[2][3][4] In addition, recent work suggests that tissue-resident B cells also form an important part of the adaptive immune defence in the lung. Many studies have focused on tissue-resident T cells (Trm cells) within lung tissues, and these adaptive immune cells have been shown to play an important part in host defence against a variety of pulmonary infections.…”

T Lymphocytes as Measurable Targets of Protection and Vaccination Against Viral Disorders

“…This RSV F subunit targeting vaccine has been demonstrated to elicit the expression of circulating neutralizing antibodies against RSV (Glenn et al, 2016). Toward the development of future adaptive immunity-inducing RSV vaccines, it has been demonstrated that the transfer of airway-resident T cells protect against RSV, where it has been suggested that, to lessen the burden of T cellemediated damage to airways, the induction of lung tissue T cells should be the focus of vaccine development (Kinnear et al, 2018).…”