CD8+ T Cell Responses in Bronchoalveolar Lavage Fluid and Peripheral Blood Mononuclear Cells of Infants with Severe Primary Respiratory Syncytial Virus Infections

Abstract

A protective role for CD8+ T cells during viral infections is generally accepted, but little is known about how CD8+ T cell responses develop during primary infections in infants, their efficacy, and how memory is established after viral clearance. We studied CD8+ T cell responses in bronchoalveolar lavage (BAL) samples and blood of infants with a severe primary respiratory syncytial virus (RSV) infection. RSV-specific CD8+ T cells with an activated effector cell phenotype: CD27+CD28+CD45RO+CCR7−CD38+HLA-DR+Granzyme B+CD127− could be identified in BAL and blood. A high proportion of these CD8+ T cells proliferated and functionally responded upon in vitro stimulation with RSV Ag. Thus, despite the very young age of the patients, a robust systemic virus-specific CD8+ T cell response was elicited against a localized respiratory infection. RSV-specific T cell numbers as well as the total number of activated effector type CD8+ T cells peaked in blood around day 9–12 after the onset of primary symptoms, i.e., at the time of recovery. The lack of a correlation between RSV-specific T cell numbers and parameters of disease severity make a prominent role in immune pathology unlikely, in contrast the T cells might be involved in the recovery process.

Airway CD8+T Cells Are Associated with Lung Injury during Infant Viral Respiratory Tract Infection

“…Lymphocytes were present as low-frequency, but measurable, populations in airway aspirates, representing less than 5% of the total cells ( Figure 1, bottom row) in both uninfected and infected patients. This cellular composition of airway aspirates is similar to that found in bronchoalveolar lavage fluid of infants (19), and therefore tracheal aspirates represent an accurate sampling of the airway environment using a noninvasive approach that is part of routine clinical care.…”

“…1 T cells in infants and an association with viral clearance and/or recovery (19,21,31). However, by integrating our results on airway T cell content from multiple VRTI with disease severity and ALI, we reveal an association of the persistence of airway CD8 1 T cells with ALI and disease progression.…”

Controlled human infection with RSV: The opportunities of experimental challenge

“…T cell-inducing vaccines have a number of theoretical advantages, including the amelioration of disease if infection does occur; the potential to protect against multiple strains of the same virus in the face of some antigenic change; and helping B cells produce high affinity antibodies [43]. However, in primary RSV infection, T cells arise late and are not thought to contribute significantly to protection [7]. Furthermore, in mouse models they have been shown to cause immunopathology [44].…”

“…infantile bronchiolitis and have been important in dissecting the mechanisms underlying vaccine-enhanced disease, so far none have been shown to adequately replicate RSV disease in elderly adults, who become increasingly susceptible to severe disease with age despite multiple prior infections that induce partial protective immunity [6]. In contrast, studies of hospitalised children and high-risk adults allow observations of natural disease in high-risk patients of greatest interest, but due to the several day incubation period of the virus coupled with frequent delays in diagnosis, it is only possible to assess patients as they approach or are recovering from peak illness [7,8]. While therapeutic trials in hospitalised children and adults are possible, variability of infecting viruses, co-infections, co-morbidities, medical interventions and atypical disease presentations limit interpretation.…”

Lymphocyte Subsets in Bronchoalveolar Lavage Fluid of Children with Lung Infiltrates

“…Lymphocyte subsets were measured in the collected BAL fluid. Information about the patients who underwent bronchoscopy and BAL was collected, including demography, country, age and gender, as in other studies (5).…”