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Fatal meningitis following lymphocytic choriomeningitis virus infection reflects delayed-type hypersensitivity rather
Abstract:
Fatal meningitis following intracerebral inoculation of lymphocytic choriomeningitis virus (LCMV) reflects an immunopathological lesion believed to be mediated by cytotoxic T cells. The results presented here demonstrate that pretreatment with cyclophosphamide (Cy; 150 mg/kg body weight) 2 days before intracerebral infection significantly reduced the lethality of the infection. However, this treatment did not impair the antiviral cytotoxic response as measured in the spleen. On the other hand, virus-specific delayed-type hypersensitivity (DTH) was significantly reduced. This reduction seems to be the result of a Cy-induced lack of non-committed ancillary cells since: (1) virus-primed spleen cells from Cy-pretreated donors conferred normal LCMV-specific DTH to naive recipients; (2) transfer of virus-primed spleen cells from untreated donors did not increase the suppressed DTH response of the Cy-pretreated mice; and (3) inoculation of irrelevant antigen and antigen-primed spleen cells into the footpads of Cy-pretreated, infected mice resulted in a significantly reduced footpad swelling as compared with untreated, infected controls. Taken together, these results indicate that LCMV-induced meningitis does not solely represent T-cell-mediated cytotoxicity in vivo but that a fatal outcome of the infection critically involves not only effector T cells but also ancillary cells.
Insights
Cyclophosphamide (Cy) pretreatment reduced fatal lymphocytic choriomeningitis virus (LCMV) meningitis lethality by suppressing delayed-type hypersensitivity (DTH) without impairing cytotoxic T cells, indicating ancillary cells are crucial for fatal outcomes.
Area of Science:
- Immunology
- Virology
- Neuroscience
Background:
- Fatal meningitis caused by lymphocytic choriomeningitis virus (LCMV) is an immunopathological condition.
- This condition is primarily attributed to the action of cytotoxic T cells.
- Understanding the immune mechanisms involved is crucial for developing therapeutic strategies.
Purpose of the Study:
- To investigate the role of ancillary cells in LCMV-induced meningitis.
- To determine the effect of cyclophosphamide (Cy) pretreatment on LCMV infection lethality and immune responses.
- To elucidate the contribution of T-cell cytotoxicity and ancillary cells in fatal meningitis.
Main Methods:
- Mice were pretreated with cyclophosphamide (Cy) 2 days before intracerebral LCMV infection.
- Lethality, antiviral cytotoxic T cell response in the spleen, and virus-specific delayed-type hypersensitivity (DTH) were assessed.
- Experiments involving adoptive transfer of spleen cells and inoculation of irrelevant antigens were conducted.
Main Results:
- Cy pretreatment significantly reduced LCMV infection lethality but did not impair splenic cytotoxic T cell responses.
- Virus-specific DTH was significantly reduced in Cy-pretreated mice, suggesting a role for ancillary cells.
- Adoptive transfer experiments confirmed that Cy-induced suppression of DTH was due to a lack of non-committed ancillary cells.
Conclusions:
- Fatal LCMV-induced meningitis involves more than just T-cell-mediated cytotoxicity.
- Ancillary cells play a critical role in the fatal outcome of LCMV infection.
- Targeting ancillary cells may offer a therapeutic approach for managing LCMV meningitis.