Abstract
Cells of the human immune system are important target cells for measles virus (MeV) infection and infection of these cells may contribute to the immunologic abnormalities and immune suppression that characterize measles. The thymus is the site for production of naïve T lymphocytes and is infected during measles. To determine which populations of thymocytes are susceptible to MeV infection and whether strains of MeV differ in their ability to infect thymocytes, we used ex vivo human thymus organ cultures to assess the relative susceptibility of different subpopulations of thymocytes to infection with wild type and vaccine strains of MeV. Thymocytes were susceptible to MeV infection with the most replication in immature CD4+CD8+ double positive cells. Susceptibility correlated with the level of expression of the MeV receptor CD150. Wild type strains of MeV infected thymocytes more efficiently than the Edmonston vaccine strain. Thymus cultures from children ≥3 years of age were less susceptible to MeV infection than cultures from children 5 to 15 months of age. Resistance in one 7 year-old child was associated with production of interferon-gamma suggesting that vaccination may result in MeV-specific memory T cells in the thymus. We conclude that immature thymocytes are susceptible to MeV infection and thymocyte infection may contribute to the immunologic abnormalities associated with measles.
Highlights
Measles continues to be an important cause of child morbidity and mortality worldwide and many aspects of the pathogenesis of the disease remain poorly understood [1,2]
measles virus (MeV) Infection of Thymocytes in Thymus organ cultures (TOCs) To determine the susceptibility of thymocytes to MeV infection, TOCs were inoculated with Chi-1 or control culture supernatant fluid, and thymocytes were monitored for 6 days for expression of intracellular MeV N protein by flow cytometry (Fig. 1)
Thymus organ cultures from older children were often resistant to MeV infection and in one child this was associated with production of IFN-gamma within the culture
Summary
Measles continues to be an important cause of child morbidity and mortality worldwide and many aspects of the pathogenesis of the disease remain poorly understood [1,2]. Lymphopenia is characteristic of acute measles [5] and dysfunction of infected cells may contribute to immunologic abnormalities that include depressed delayed type hypersensitivity skin test responses [6,7,8], decreased mitogen-induced lymphoproliferation [9,10,11] and increased susceptibility to other infections [12,13] and autoimmune disease [14]. Within these mononuclear cell populations, some subsets of cells are more susceptible to infection than others and this varies with virus strain [15,16]. Identification of the cells of the immune system that are infected by wild type and vaccine strains of MeV is important for understanding the effects of MeV infection on the immune system
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