title: Characterization of thymic involution induced by murine cytomegalovirus infection.
abstract: Infection of BALB/c mice with murine cytomegalovirus (MCMV) decreased the numbers of cells recovered from the thymus by 80-90% after 4-7 days, although less than 10 thymocytes per million were productively infected with the virus. A loss of cortical thymocytes was evident in histologic sections and correlated with depletion of CD4+ CD8+ cells. Thymic involution was minimal in C57BL/6 mice. This resistance was not H-2b-associated, as BALB.B (H-2b) mice were severely affected. In CXB recombinant inbred mice, thymic involution and MCMV replication co-segregated with atrophy and infection of the spleen and bone marrow. This suggests common regulation by natural killer (NK)1.1+ cells, consistent with the enhanced thymic involution demonstrated in NK-deficient bg/bg mice. However, CD4- CD8- cells were not depleted, so bone marrow hypoplasia may not be the proximal cause of thymic involution. MCMV infection activated CD4+, CD8+ and CD4+ CD8+ thymocytes, as expression of MEL14, major histocompatibility complex class I (H-2) and Sca-1 antigens increased on these cells. In vitro lymphoproliferation and interleukin (IL)-3 release were enhanced in unseparated and CD4(+)-enriched thymus preparations. Maturation of the thymus population was also evident from the high frequencies of single positive CD4+ and CD8+ cells and the decline in Sca-2 expression. However, unlike peripheral T cells, thymocytes from infected mice did not release IL-2. The results suggest that thymic involution accelerates the transit of cells through the thymus. The possibility that this impairs the elimination of autoreactive T cells within the thymus and promotes the autoimmune manifestations of MCMV disease is discussed.
authors.affiliation: Department of Microbiology, University of Western Australia, Nedlands.
authors.forename: P
authors.initials: P
authors.lastname: Price
authors.forename: S D
authors.initials: SD
authors.lastname: Olver
authors.forename: A E
authors.initials: AE
authors.lastname: Gibbons
authors.forename: H K
authors.initials: HK
authors.lastname: Teo
authors.forename: G R
authors.initials: GR
authors.lastname: Shellam
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000032:analysis; D001284:Atrophy; D001327:Autoimmune Diseases / Q000209:etiology*; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000032:analysis; D002465:Cell Movement; D003586:Cytomegalovirus Infections / Q000150:complications / Q000473:pathology*; D020022:Genetic Predisposition to Disease; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology; D016130:Immunophenotyping; D007377:Interleukin-3 / Q000378:metabolism; D019041:L-Selectin; D007958:Leukocyte Count; D008213:Lymphocyte Activation; D016177:Macrophage-1 Antigen / Q000032:analysis; D008565:Membrane Proteins / Q000032:analysis; D051379:Mice; D008807:Mice, Inbred BALB C / Q000235:genetics / Q000276:immunology; D008810:Mice, Inbred C57BL / Q000235:genetics / Q000276:immunology; D008815:Mice, Inbred Strains / Q000235:genetics / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000473:pathology*; D013602:T-Lymphocytes, Cytotoxic / Q000473:pathology; D013950:Thymus Gland / Q000473:pathology*
chemical_list: D000950:Antigens, Ly; D015815:Cell Adhesion Molecules; D006183:H-2 Antigens; D007377:Interleukin-3; C074650:Ly6a protein, mouse; D016177:Macrophage-1 Antigen; D008565:Membrane Proteins; D019041:L-Selectin