Mucosal T cell distribution during infection with respiratory syncytial virus

Abstract

Groups of 12-week-old Balb/c mice were inoculated intranasally with respiratory syncytial virus (RSV) and sacrificed at regular intervals after infection. T lymphocyte subset distribution was determined in lung tissue, bronchoalveolar lavage (BAL), peripheral blood, and spleen by means of flow cytometry employing monoclonal antibodies against the T cell membrane antigens Thy1.2 (pan-T), Ly2 (CD8), and L3T4 (CD4). Thy1.2+ cells increased in the lung from 35.4% of total lymphocytes before infection to 47.6% on day 7 after infection. This increase was largely accounted for by an increase in Ly2+ cells, which manifested a rise from 7.8% preinfection to 19.8% on day 7. The level of L3T4+ cells remained constant (27.9% preinfection vs. 25.2% on day 7). The L3T4+/Ly2+ ratio in the lungs reached a nadir 7 days post infection (1.5 vs. 3.5 before infection). The total cell count in BAL increased more than tenfold during the first week after infection. At the same time Thy1.2+ cells in the BAL increased from 41.1% of total lymphocytes on day 1 to 85.3% on day 7. Ly2+ influx was the most important (5.8% on day 1 vs. 41.1% on day 7). L3T4+ cell levels increased from 17.2% on day 1 to 40.1% on day 7. RSV-specific lymphocyte transformation was observed in BAL and blood but not in the lung tissue and spleen on day 7 postinfection. The disappearance of infectious virus in the lung correlated directly to the peak appearance of Ly2+ T cells in the lung tissue and BAL.

T cell redistribution kinetics after secondary infection of BALB/c mice with respiratory syncytial virus

“…The cytotoxic response is maximal 7-9 days after infection [18], mainly carried by CD8+ cells [4,9] and of major importance for both viral clearance and pathogenesis of disease [8,9]. Recently, flow cytometry studies defined in more detail the phenotypic characteristics ofthe T cells activated and attracted to the lungs after primary infection with RSV [5,6,19].…”

“…The spleen was removed aseptically and transferred immediately in Minimal Essential Medium with 2 mM glutamine, 100 U/ml penicillin and 100 /ig/ml streptomycin (EMEM) (GiBCO, Grand Island, NY). BAL was performed as described previously [5].…”

“…Nadal et al [3] showed significant redistribution of mucosal antibody-producing cells to the lungs of severe combined immunodeficient (SCID) mice reconstituted with human tonsillar and peripheral blood lymphocytes and challenged subsequently with RSV. T cells have been demonstrated in lung tissue after primary RSV infection by several investigators [4,5]. Moreover, T cells can be recovered from the bronchoalveolar lavage (BAL) of laboratory animals [5,6] and patients during acute RSV infection [7].…”

“…T cells have been demonstrated in lung tissue after primary RSV infection by several investigators [4,5]. Moreover, T cells can be recovered from the bronchoalveolar lavage (BAL) of laboratory animals [5,6] and patients during acute RSV infection [7].…”

“…The mouse model of RSV infection has given us the opportunity to study the lymphocyte traffic and the kinetics of T cell redistribution after primary infection with RSV [5]. The present study was undertaken to characterize T cell subset redistribution patterns in systemic and mucosal tissues after reinfection with RSV.…”