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Coccidioidal antigen reactive CD4+ T-lymphocytes in the cerebrospinal fluid in coccidioides immitis meningitis
T L Vollmer1, C Gaiser, R L Dell'Oca
1Department of Neurology, Yale School of Medicine, New Haven, CT, USA.
Insights
Coccidioides immitis meningitis triggers a strong antigen-specific immune response in cerebrospinal fluid (CSF) T-cells, detectable even in remission. CSF T-cell assays show diagnostic potential for this fungal meningitis.
Area of Science:
- Immunology
- Infectious Diseases
- Neurology
Background:
- Coccidioides immitis meningitis is a serious fungal infection affecting the central nervous system.
- Understanding the immune response within the cerebrospinal fluid (CSF) is crucial for diagnosis and management.
Purpose of the Study:
- To investigate the antigen-specific immune response of CSF lymphocytes in Coccidioides immitis meningitis.
- To evaluate the diagnostic potential of CSF T-cell proliferation assays for this condition.
Main Methods:
- In vitro stimulation of CSF lymphocytes with C. immitis antigens.
- Comparison of CSF lymphocyte responses with autologous peripheral blood mononuclear cells.
- Flow cytometry (fluorescence-activated cell sorting) to analyze immune cell populations (CD3+, CD4+, CD3+/HLA-DR+).
Main Results:
- CSF lymphocytes showed a significant antigen-specific response to C. immitis.
- Responses were detected early in the disease and during remission, and were stronger in CSF than peripheral blood.
- Increased percentages of T-cells (CD3+), helper/inducer T-cells (CD4+), and activated T-cells (CD3+/HLA-DR+) were found in CSF.
- The CD4+ lymphocyte subset was the primary source of the antigen-specific proliferative response.
Conclusions:
- CSF T-cell responses are a key feature of Coccidioides immitis meningitis.
- CSF T-cell proliferation assays may serve as a valuable diagnostic tool for Coccidioides immitis meningitis.
Abstract:
CSF lymphocytes from patients with Coccidioides immitis meningitis exhibited a significant antigen-specific response to in vitro stimulation with C. immitis antigens. In some patients, lesser responses to control antigens (Candida and PPD) were also detected. Antigen-specific responses by CSF lymphocytes were seen early in the course of this disease as well as several years after patients had entered remission. When compared to CSF cells, the response of autologous peripheral blood mononuclear cells was similar but of a much smaller magnitude and at times undetectable. Fluorescence activated cell sorting revealed an increased percentage of CD3+ (T-cells), CD4+ (helper/inducer) and CD3+/HLA-DR+ (activated T-cell) cells in the CSF of C. immitis meningitis patients compared to their blood. Most of the antigen-specific proliferative response resided in the CD4+ lymphocyte subset. CSF T-cell proliferation assays may have a role in the diagnosis of C. immitis meningitis.