Reduced in Vitro Response of CSF Lymphocytes to Mitogen Stimulation in Multiple Sclerosis

Kam‐Hansen, Slavenka; Link, Hans; Frydén, Aril; Möller, Erna

doi:10.1111/j.1365-3083.1979.tb03271.x

Cited by 34 publications

(14 citation statements)

References 15 publications

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“…This disparity may be explained by the different pathways of activation fol lowed by T cells after stimulation with these molecules. The low sHLA secretion by MS PBL on PHA activation could be a consequence of prolonged sensitization to an as yet unidentified antigen [14], The normal cell prolifera tion in our cases, similar to results published previously [7], does not invalidate this hypothesis since these events are independent of each other [9]. Since MS lymphocytes seem to secrete elevated levels of y-interferon [15,16], another explanation for our findings is that this molecule could inhibit sHLA secretion in our patients, an effect that we have previously found in vitro in the normal pop ulation [unpubl.…”

Section: Discussionmentioning

confidence: 99%

Soluble Class I Antigen Secretion by Peripheral Blood Lymphocytes in Multiple Sclerosis

Alvarez‐Cermeño

Brieva²,

Villar³

et al. 1993

Eur Neurol

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We have quantified the soluble class I antigen (sHLA) secretion by peripheral blood lymphocytes of 26 multiple sclerosis (MS) patients. Thirteen of them were in a stable phase of the disease, 6 on relapse and 7 suffered from a progressive MS. sHLA secretion was reduced in the presence or absence of phytohemagglutinin in patients with either active or stable MS, being normal after stimulation with a monoclonal antibody anti-CD3. In MS patients, lymphocyte proliferation and immunoglobulin secretion were found to be similar to those of 29 healthy blood donors who comprised the group of controls. These results reflect systemic anomalies in the cell activation process in MS, which seem to be independent of the disease activity. Whether these alterations are specific to MS or are common to other inflammatory CNS diseases remains to be elucidated.

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Section: Discussionmentioning

confidence: 99%

Soluble Class I Antigen Secretion by Peripheral Blood Lymphocytes in Multiple Sclerosis

Alvarez‐Cermeño

Brieva²,

Villar³

et al. 1993

Eur Neurol

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“…It has been reported that CSF mononuclear cells respond poorly to mitogens (Kam-Hansen et al 1979), Similarly, it has been found that synovial fluid cells from patients with rheumatoid arthritis also proliferate poorly to mitogens (Stratton et al 1978). In the case of synovial fluid, stimulation was depressed via the CD3 T-cell receptor (TCR) complex, and this could be reversed by the addition of either IL-1 or IL-2 (Lotz et aL 1986).…”

Section: Activation Pathways Of Csf T Cellsmentioning

confidence: 99%

T Cells in Multiple Sclerosis and Inflammatory Central Nervous System Diseases

Hafler¹,

Weiner²

1987

Immunological Reviews

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Using murine monoclonal antibodies to mark total T cells, we have found rapid migration of T cells into the CSF in progressive multiple sclerosis patients, suggesting that the ongoing inflammatory responses in the CNS may depend on the continued movement of cells from the periphery into the target organ. Cloning experiments have indicated that the T cells present in the CSF during viral and post-viral encephalomyelitis represent sequestered populations of antigen-specific cells. In more chronic disease processes, these cells may also have restricted clonality as measured by the frequency of different T-cell receptor gene rearrangements on Southern blotting. It is known that there is restricted clonality of the B-cell immunoglobulin response in the CSF compartment with inflammatory CNS diseases, and with infections the majority of these so-called oligoclonal antibodies are directed against the exciting antigen and are synthesized in the CNS. Although we believe that T cells in the CNS originate from the blood, during the course of an inflammatory response the antigen and clonally-restricted populations found in the CSF may represent either selective migration or selective accumulation in the CNS. Selective migration might occur at the endothelial barrier as these cells can express Class II MHC antigens and act as antigen-presenting cells in the CNS (McCarron et al. 1985). Selective accumulation of T cells in the CNS might occur after non-specific migration of cells into the CNS followed by proliferation and expansion of T cells that have been induced by antigens in the brain. Antigen-presenting cells that are present in situ, such as astrocytes, may also play a role in the selective expansion of T cells in the CSF (Fontana et al. 1984). Alternatively, it is possible that T cells are induced to expand in the target CNS tissue non-specifically, e.g., via the CD2 pathway. In this regard, we have observed that CSF T cells exhibit alterations in stimulation by anti-T112 + anti-T113 monoclonal antibodies. The mechanism of damage to CNS tissue by immune cells is essentially unknown. For example there are no clear links between antibodies present in the CNS and CNS damage in SSPE where high titers of anti-measles antibodies are present. Whereas we did not observe high frequencies of measles-reactive cells in the CSF of a subject with SSPE, we did observe MHC non-restricted cytotoxic T cells which expressed TCR-gamma chains rather than alpha-beta chains.(ABSTRACT TRUNCATED AT 400 WORDS)

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“…Merrill et al (13) demonstrated loss of natural killer cell activity in MS CSF, which suggests that MS CSF lymphocytes may be different from cells seen in control CSF. Other laboratories have noted the presence of MS spinal fluid lymphocytes that are reactive to myelin basic protein (14), measles antigen (15-), mitogens (16), and alloantigens (17). Thus, there are large numbers of immunocompetent cells in the CSF of MS patients, and these cells may be different than cells seen in the CSF of patients with other neurologic diseases.…”

Section: Introductionmentioning

confidence: 99%

Spinal fluid lymphocytes responsive to autologous and allogeneic cells in multiple sclerosis and control individuals.

Birnbaum¹,

Kotilinek²,

Schwartz³

et al. 1984

J. Clin. Invest.

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Abstract. Spinal fluid lymphocytes from multiple sclerosis (MS) patients and controls were stimulated with either autologous non-T cells or with allogeneic non-T cells followed by stimulation with autologous non-T lymphocytes. Cells responding to these stimuli were cloned and their proliferative responses to autologous and allogeneic MS and normal non-T cells were measured. Large numbers of clones with specific patterns of reaction to both autologous and allogeneic cells were obtained from lymphocytes in MS cerebrospinal fluid (CSF), but only occasionally from cells in control CSF. Patterns of responses among clones from a particular CSF were similar and often identical, which suggested that cells in MS CSF were relatively restricted in their specificities. Surface antigen phenotyping of the clones showed them to be predominantly OKT4+, with 13% OKT8+ and 11% OKT4+8+. Peripheral T cells that were stimulated and cultured in parallel with CSF cells were different in that they usually did not give rise to as many clones nor were their patterns of response similar. Many CSF clones were heteroclitic, that is they responded to particular allogeneic cells but not autologous cells. Lymphocytes in MS CSF thus appear to represent a selected population of cells with a high frequency of responsiveness to autologous and allogeneic antigens. Such responses may be evidence for immune regulation within the central nervous system or could represent responses to altered-self antigens.Portions of this work were presented in abstract form at the

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Reduced in Vitro Response of CSF Lymphocytes to Mitogen Stimulation in Multiple Sclerosis

Cited by 34 publications

References 15 publications

Soluble Class I Antigen Secretion by Peripheral Blood Lymphocytes in Multiple Sclerosis

Soluble Class I Antigen Secretion by Peripheral Blood Lymphocytes in Multiple Sclerosis

T Cells in Multiple Sclerosis and Inflammatory Central Nervous System Diseases

Spinal fluid lymphocytes responsive to autologous and allogeneic cells in multiple sclerosis and control individuals.

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