Dynamics of Human Respiratory Virus-Specific CD8+ T Cell Responses in Blood and Airways during Episodes of Common Cold

Abstract

We determined the dynamics of CD8+ T cells specific for influenza virus and respiratory syncytial virus in blood and tracheostoma aspirates of children during the course of respiratory infections. We showed that during localized respiratory infections the ratio of activated effector CD8+ T cells to resting memory/naive CD8+ T cells in peripheral blood increased significantly. Furthermore, the number of effector/memory T cells specific for respiratory viruses declined in blood and increased in the airways, suggesting that these T cells redistributed from blood to airways. T cells specific for the infecting virus were present in the airways for longer periods at increased levels than nonspecifically recruited bystander T cells. After clearance of the infection, the ratio of resting memory and naive CD8+ T cells normalized in peripheral blood and also memory T cell numbers specific for unrelated viruses that declined during the infection due to bystander recruitment were restored. Taken together, these results showed a significant systemic T cell response during relatively mild secondary infections and extensive dynamics of virus-specific and nonspecific Ag-experienced T cells.

CD8 T-Cell Response to Respiratory Syncytial Virus Infection

“…However, the frequency of RSV-specific CD8 T cells in the BAL increased during convalescence suggesting that these cells formed a memory CD8 T-cell population. Additional work by the same group also revealed similar results from tracheal aspirate samples [44]. The RSV-specific CD8 T-cell response remained low comprising less than 2% of total CD8 T cells for the epitope assessed.…”

“…CD8 T cells from C57BL/6 mice primarily recognize the immunodominant M 187-195 epitope. Although numerous CD8 T-cell epitopes have been identified in humans, in contrast to mice, the frequency of responding cells that can be detected in the airways is typically very low (<2%) [43,44]. F 551-559 IAVGLLLYC A2 C12 [58] M 195-203 IPYSGLLLV A2 B51 [46] M 229-237 YLEKESIYY A2 A1 [46] M2 64-72 AELDRTEEY A2 B44 [46] M2 151-159 RLPADVLKK A2 A3 [46] N 255-263 QVMLRWGVL A2 B8 [57] NS2 41 Additional human CD8 T-cell epitopes against RSV have been identified using computational prediction and MHC binding assays, but require further confirmation [59].…”

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

“…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.…”

“…The overall functional capacities of human infant T cells as being skewed toward Th2 or antiinflammatory responses (8) is largely derived from studies of umbilical cord blood (24)(25)(26). Measuring the in vivo infant immune response to VRTI has been more challenging, and has involved characterization of cells and cytokines in peripheral blood (6,21,27,28), nasopharyngeal washes (29,30), or tracheal aspirates (31,32). However, sampling remains limited, and unifying immune parameters related to disease outcome and severity has not emerged.…”

Characterization of the Human CD8+T Cell Response following Infection with 2009 Pandemic Influenza H1N1 Virus

“…Once the virus infection is cleared, the CTL response contracts rapidly, but memory T cells persist, which can be recalled upon a subsequent infection with influenza A virus (8). The rapid decrease of virus-specific CD8 ϩ T cells from the blood may reflect migration of these cells to the site of infection (12). It has been reported that the frequency of Tm ϩ CD8 ϩ T cell is low after 2009 H1N1 influenza virus infection (6).…”