Development of in Vitro Correlates of Cell-Mediated Immunity to Respiratory Syncytial Virus Infection in Humans

Abstract

Groups of infants and children with infections due to respiratory syncytial virus (RSV) were tested at the onset of illness and one, two, and five months later for the presence of RSV-specific cell-mediated immunity, as determined by in vitro lymphocyte transformation (LTF) activity, and for complement-fixing (CF) antibody. An LTF response specific for RSV was observed in 65 % of patients, and the response was largely associated with E-rosette-forming thymus-derived (T) lymphocytes. A significant cell-mediated immune response was observed in 78% of patients six months of age or younger, whereas only 46% of patients older than six months exhibited such responses. The difference between the mean stimulation index of the maximal LTF response in the two age groups was statistically significant (P less than 0.05). On the other hand, a fourfold or greater rise in titers of CF antibody was observed in only 22% of patients six months of age or younger, whereas significant rises in antibody activity were observed in 50% of subjects older than six months. In view of the fact that RSV infection is most severe in the young infant, these observations raise the possibility that cell-mediated hypersensitivity reactions may be related to the pathogenesis of RSV infection of infants.

Analysis of the local and systemic immune responses induced in BALB/c mice by experimental respiratory syncytial virus infection

“…These studies have consistently described convalescent stage PBL responsiveness to in vitro RS virus challenge (Scott et al, 1978;Welliver et al, 1979;Cranage & Gardner, 1980;Mito et al, 1984). However, there has been some disagreement over whether this responsiveness may be detected during the acute phase of illness.…”

Cytotoxic Lymphocytes in the Lungs of Mice Infected with Respiratory Syncytial Virus

“…In addition, CF and neutralizing antibodies induced by a formalin-inactivated vaccine failed to protect against either infection or disease (Kapikian et al, 1969;Kim et al, 1969;Fulginiti et al, 1969). These discrepancies have stimulated investigations into the role of cell-mediated immunity in RSV infection using lymphocyte transformation and leukocyte migration inhibition tests (Scott et al, 1978 ;Bertotto et al, 1980). The importance of cytotoxic T-lymphocytes (CTL) in recovery from many viral infections, including those caused by other paramyxoviruses, has also encouraged investigations into their role in RSV infections.…”

Steroids Fail to Down-Regulate Respiratory Syncytial Virus-Induced IL-8 Secretion in Infants

“…In contrast, neonatal monocyte-derived macrophages and lymphocytes secrete less IFN-␥ than adult cells (16) and PBMC secrete less IL-3, IL-15, and granulocyte-macrophage colony stimulating factor (27). The data concerning agedependent responses to RSV are inconsistent with both increased and reduced cell-mediated immunity reported (28,29). Such differences may be stimulus and mediator specific.…”