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Characterization of thymic involution induced by murine cytomegalovirus infection
Author(s) -
PRICE PATRICIA,
OLVER STUART D.,
GIBBONS ANNE E.,
TEO HUI KUN,
SHELLAM GEOFFREY R.
Publication year - 1993
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1038/icb.1993.18
Subject(s) - thymic involution , involution (esoterism) , biology , cd8 , thymocyte , immunology , population , spleen , t lymphocyte , bone marrow , antigen , medicine , endocrinology , t cell , immune system , consciousness , environmental health , neuroscience
Summary 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‐2 b ‐associated, as BALB.B (H‐2 b ) 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.