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Phenotypic analysis of the inflammatory exudate in murine lymphocytic choriomeningitis
Abstract:
The massive inflammation of the cerebrospinal fluid (CSF) which occurs in adult mice injected with lymphocytic choriomeningitis virus (LCMV) has been analyzed by flow microfluorometry (FMF). The great majority of the T cells detected by direct examination of freshly obtained CSF were found to be Lyt-2+, with an almost total absence of L3T4+ lymphocytes. The Lyt-2/L3T4 ratio of lymphocytes in blood was within normal limits. Predominance of the Lyt-2+ subset was confirmed by culturing the CSF cells after mitogenic stimulation. In addition, the T lymphocytes in CSF of cyclophosphamide-suppressed, virus-infected recipients that had been injected 4 d previously with LCMV-immune spleen cells were almost entirely donor Lyt-2+ cells, while the nonlymphoid elements were exclusively of host origin. However this pattern of donor and host T cell distribution was reversed when the LCMV-infected recipients were not immunosuppressed. The frequency of LCMV-specific CTL precursors in CSF taken immediately before the development of symptoms was as low as 1:3,000 cells. Thus most of the T lymphocytes extravasating into the CSF of mice with LCM are passive participants recruited as a consequence of the function of relatively few LCMV-specific effector T cells. The dominance of the Lyt-2+ T cell subset in the CSF of mice with LCM is intriguing.
Insights
In mice with lymphocytic choriomeningitis virus (LCMV) infection, cerebrospinal fluid (CSF) shows a high number of Lyt-2+ T cells, indicating their passive recruitment during inflammation.
Area of Science:
- Immunology
- Neuroscience
- Virology
Background:
- Lymphocytic choriomeningitis virus (LCMV) infection in adult mice causes significant cerebrospinal fluid (CSF) inflammation.
- T cell subsets play crucial roles in immune responses within the central nervous system.
Purpose of the Study:
- To analyze the T cell populations in the CSF during LCMV infection.
- To investigate the role and origin of T cells in the inflamed CSF.
Main Methods:
- Flow microfluorometry (FMF) analysis of CSF and blood.
- Mitogenic stimulation and cell culturing of CSF lymphocytes.
- Analysis of T cell distribution in immunosuppressed and non-immunosuppressed recipients.
Main Results:
- CSF predominantly contained Lyt-2+ T cells, with a scarcity of L3T4+ lymphocytes.
- The Lyt-2/L3T4 ratio in blood remained normal.
- In immunosuppressed recipients, adoptively transferred T cells were mainly donor Lyt-2+ cells, while non-lymphoid cells were host-derived.
- This distribution pattern reversed in non-immunosuppressed recipients.
- LCMV-specific cytotoxic T lymphocyte (CTL) precursors were rare in early-stage CSF.
Conclusions:
- The majority of T lymphocytes in the CSF during LCMV infection are passively recruited.
- The dominance of Lyt-2+ T cells in CSF suggests a specific inflammatory response pattern.
- Few effector T cells drive the recruitment of numerous bystander T cells into the CSF.