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T cell lines established from multiple sclerosis cerebrospinal fluid T cells using human retroviruses
J E Merrill1, J M Kagan, I Schmid
1Department of Neurology, UCLA School of Medicine 90024.
Journal of Neuroimmunology
|February 1, 1989
Summary
Researchers transformed cerebrospinal fluid lymphocytes from multiple sclerosis patients using human T cell leukemia/lymphoma virus (HTLV). The resulting cell lines exhibit unique characteristics and suppress immunoglobulin production, offering a valuable tool for multiple sclerosis research.
Area of Science:
- Immunology
- Virology
- Neuroscience
Background:
- Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system.
- Cerebrospinal fluid (CSF) lymphocytes offer a unique window into the immunopathology of MS.
- Human T cell leukemia/lymphoma virus (HTLV) can infect and transform lymphocytes.
Purpose of the Study:
- To create and characterize novel cell lines from MS patient CSF lymphocytes transformed by HTLV.
- To assess the functional capabilities and cytokine production of these unique cell lines.
- To evaluate the potential of these cell lines as research tools in MS studies.
Main Methods:
- Transformation of CSF lymphocytes from MS patients with HTLV I and HTLV II.
- Cell surface phenotyping using flow cytometry (CD4, CD8, TA1, HLA-DR, TAC/CD25, OKT10/CD38).
- Functional assays including natural killer (NK) activity, antibody-dependent cellular cytotoxicity (ADCC), proliferation assays, and assessment of immunoglobulin production suppression.
Main Results:
- HTLV-transformed cell lines were predominantly CD4+ helper/inducer phenotype, with some HTLV II lines containing CD8+ cells.
- The cell lines displayed activated markers (TA1+, HLA-DR+, TAC+) but lacked OKT10 expression.
- Lines showed no NK activity, modest ADCC, poor proliferative responses, and suppressed pokeweed mitogen (PWM)-driven immunoglobulin production.
- Cell lines produced gamma-interferon (IFN-γ), lymphotoxin (LT), IL-1-like factor, glial growth promoting factor (GGPF), and IL6.
- HTLV I lines were nonresponsive or suppressed by interleukin 2 (IL2), while HTLV II lines responded to IL2.
Conclusions:
- HTLV-transformed MS CSF lymphocyte cell lines are a valuable, indefinitely growing resource for studying MS immunopathology.
- These cell lines possess unique functional properties, including the suppression of B cell immunoglobulin production.
- The ability to grow without feeder layers or IL2 and to be cloned makes these lines advantageous for research.