CD8+ T cell responses in bronchoalveolar lavage fluid and peripheral blood mononuclear cells of infants with severe primary respiratory syncytial virus infections (original) (raw)

2007, Journal of Immunology

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. FIGURE 4. Kinetics of the RSV-specific CD8 ϩ T cell response in peripheral blood during a primary infection with RSV. A, Peptide-specific CD8 ϩ T cells expanded from adult PBMC in the presence of NP 306 -314 and rIL-2 respond equally well to peptide-pulsed and RSV-infected DCs showing the efficacy of RSV-infected DC to display viral epitopes. B, Partially HLA-matched RSV-infected (top row) or uninfected (second row) and peptide (NS1 33-41 KLIHLTNAL) pulsed DCs (HLA-A1, A2, B8, B15, 7.0% of the DC in the culture expressed RSV F protein at the surface) were cocultured for 5 h with PBMC of a patient (HLA-A2, A11, B8, B15). Peptide-pulsed DCs were used to stimulate PBMC samples at the time of discharge, i.e., the peak of the virus-specific response. The appearance of proliferating effector T cells (GzmB ϩ /Ki-67/CCR5 ϩ ) in the same samples is shown in rows 3 and 4.