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Mouse thymic virus (MTLV). A mammalian herpesvirus cytolytic for CD4+ (L3T4+) T lymphocytes
1Rockefeller University Laboratory Animal Research Center, New York, New York.
Abstract:
Mouse thymic virus (MTLV; ICTV designation murid herpesvirus 3) infects developing T lymphocytes of neonatal mice, causing thymic necrosis and acute immunosuppression. Infected animals shed virus indefinitely. In the present report, two-color flow cytometric analysis of T lymphocyte subpopulations defined by the markers CD4 (L3T4) and CD8 (Lyt-2) was used to determine whether MTLV was lytic for a specific thymocyte population. At peak necrosis (8-11 d after infection), numbers of CD4+8+ cells in the thymus were reduced by 80% or more as compared with controls, and CD4+8- cells were reduced by greater than 98%. The major survivors were CD4-8+ and CD4-8- lymphocytes. These data indicate that the CD4 bearing lymphocyte is a primary target for cytolysis during MTLV infection. Possible parallels between MTLV and a newly described lymphotropic human herpesvirus, human herpesvirus 6 (HHV-6/HBLV), are also suggested.
Insights
Mouse thymic virus (MTLV) primarily targets CD4+ T lymphocytes, causing significant thymic necrosis and immunosuppression in neonatal mice. This herpesvirus infection leads to a drastic reduction in specific T cell populations.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Mouse thymic virus (MTLV), also known as murid herpesvirus 3, infects developing T lymphocytes in neonatal mice.
- MTLV infection results in thymic necrosis and acute, long-term immunosuppression, with infected animals shedding the virus indefinitely.
Purpose of the Study:
- To determine if MTLV exhibits specific lysis towards a particular thymocyte subpopulation.
- To investigate the impact of MTLV infection on CD4 and CD8 T lymphocyte subpopulations.
Main Methods:
- Two-color flow cytometry was employed to analyze T lymphocyte subpopulations.
- Analysis focused on cells defined by CD4 (L3T4) and CD8 (Lyt-2) markers in infected and control neonatal mice.
Main Results:
- At 8-11 days post-infection, CD4+8+ thymocytes decreased by over 80% and CD4+8- thymocytes by over 98%.
- The primary surviving lymphocyte populations were CD4-8+ and CD4-8- cells.
- These findings strongly indicate that CD4-bearing lymphocytes are a major target for cytolysis by MTLV.
Conclusions:
- Mouse thymic virus (MTLV) preferentially lyses CD4-bearing thymocytes, leading to severe thymic atrophy and immunosuppression.
- The data suggest potential parallels between MTLV and human herpesvirus 6 (HHV-6), another lymphotropic herpesvirus.