B and T cell imbalances in CSF of patients with Hu-antibody associated PNS

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作者：Marieke de Graaf ; Janet de Beukelaar ; Jelmer Bergsma ; Jaco Kraan ; Martin van den Bent ; Markus Klimek ; Yvette van Norden ; Arinardi Kusuma ; Peter Sillevis Smitt ; Jan Willem Gratama
关键词：Paraneoplastic neurological syndromes ; Hu-antibody ; Lymphocyte subsets ; Cerebrospinal fluid ; Cancer
刊名：Journal of Neuroimmunology
出版年：2008
期刊代码：32_01655728
类别：neu
出版时间：March 2008
卷：195
期：1-2
页码：164-170
文件大小：399 K

摘要

We compared enzymatic and mechanical methods of intraprostatic lymphocyte isolation in healthy 8 to 10-week-old Sprague-Dawley rats. Mechanical isolation was chosen because of its superior preservation of surface antigens. Intraprostatic lymphocyte subsets were analyzed by flow cytometry.

Results:

Levels of prostatic αβTCR+ T cells were similar and levels of prostatic B cells were decreased 5 to 10-fold compared with those found in other tissues (p ≤0.005). Unexpectedly two-thirds of the total prostatic lymphocytes expressed the natural killer (NK) marker CD161a+. They were divided equally between NK (CD161a+αβTCR⁻) and NKT (CD161a+αβTCR+) cells. Of prostatic CD161a+ cells 50%to 60%were also CD8+. Levels of NKT cells were dramatically lower in other tissues (p ≤0.005) and they never accounted for more than 8%of total lymphocytes. The prostate contained lower levels of CD4+ T cells than all tissues except the liver (p ≤0.005) and higher levels of CD8+ T cells than any other tissue studied (p ≤0.05), resulting in an inverted CD4-to-CD8 ratio. CD45RC+CD4+αβTCR+ T cells and CD161a+CD4+αβTCR+ NKT cells were elevated in the prostate (p ≤0.02).

Conclusions:

The healthy rat prostate contains an unusually high proportion of NK and NKT cells. The balance between the CD45RC+CD4+αβTCR+ T cells, which initiate the cell mediated immune response, and CD4+ NKT cells, which can suppress autoimmunity, may be a key in understanding the resistance of Sprague-Dawley rats to chronic nonbacterial prostatitis.

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We, for the first time, analyzed T cell and natural killer (NK) cell subsets in the cerebrospinal fluid (CSF) in nine patients with human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) treated with interferon-α (IFN-α). The CD4/CD8 ratio in CSF was significantly lower after the therapy, which is mainly attributable to the significant reduction in CD4+ cells, especially CD25+CD4 and CD45RO+CD4 cell subsets. Meanwhile, NK, natural T and NKT cell subsets in the CSF remained unchanged. There was no CSF lymphocyte subset significantly associated with the clinical efficacy of IFN-α in this small-scale study, and more patients should be analyzed to ascertain the link.

Innate and adaptive cellular immunity is initiated, directed and regulated by a vast array of cell surface receptors. Attempts to harness the cellular immune system in translational settings such as immunotherapy and vaccine development require tools to accurately describe and isolate lymphocytes with specific characteristics. One such tool, flow cytometry, is undergoing a revolution in instrumentation and reagents, providing opportunities for high resolution phenotypic and functional analysis of lymphocytes. Here, we demonstrate how nine-color flow cytometry can be adapted, optimized and applied to investigate the phenotypic complexity and functional heterogeneity of human lymphocyte subsets. We provide examples of studies of adaptive T cell responses against viruses, as well as the assessment of CD1d-restricted NKT cells and NK cells. We discuss the importance of this technology for detailed investigations of lymphocyte subsets in studies of infectious diseases and cancer.

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