Age-Related Development of Human Memory T-Helper and B-Cell Responses toward Parainfluenza Virus Type-1

Abstract

Human parainfluenza-1 virus (hPIV-1) infections are a major cause of respiratory illness in young children. While children and adults are each susceptible to hPIV-1 infection, the clinical symptoms in adults are mild and hospitalizations are rare. One explanation for the differences in disease severity is that immune memory responses are simply inferior in children as compared to adults and cannot counter virus growth. Alternatively, it has been suggested that immune (particularly T-helper (TH) cell) responses toward respiratory viruses are superior in children versus older individuals, and that these responses contribute to, rather than protect from, disease symptoms. As a test of these possibilities, we analyzed hPIV-1-specific T-helper (TH) and B-cell memory responses among individuals of various ages, including children hospitalized with hPIV-1-induced croup. Experiments revealed: (1) hPIV-1-specific B-cell and class-II restricted TH-Cell proliferative responses were present in all tested adults. (2) TH-cells responded to internal viral proteins as well as to the external glycoprotein, hemagglutinin-neuraminidase. (3) Immune responses were highly cross-reactive with Sendai virus. (4) Memory B-cell and TH-cell responses were extremely poor in young children, inclusive of children tested upon hospital entry for hPIV-1-induced croup. In total, results did not support the theory that naturally induced hPIV-specific memory responses cause respiratory illness. Rather, results showed a correlation between memory and a good clinical outcome and highlighted Sendai virus as a strong candidate for an hPIV-1 vaccine.