Compartmentalization of antigen specific cytokine responses to the central nervous system in CNS borreliosis: secretion of IFN-γ predominates over IL-4 secretion in response to outer surface proteins of Lyme disease Borrelia spirochetes

Ekerfelt, Christina; Ernerudh, Jan; Bunikis, Jonas; Vrethem, Magnus; Aagesen, Jesper; Roberg, Magnus; Bergström, Sven; Forsberg, Pia

doi:10.1016/s0165-5728(97)00118-5

Cited by 62 publications

(67 citation statements)

References 32 publications

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“…Interestingly, positive responses against the six candidate epitope peptides were significantly more common in CSF compared with blood, which is in line with compartmentalization of the immune response to CNS, as noted previously in neuroborreliosis [16]. In order to perform epitope mapping for CSF cells, however, pleocytosis or large amount of CSF is required for mapping the entire OspA sequence.…”

Section: Discussionsupporting

confidence: 81%

T‐Cell Epitope Mapping of the Borrelia garinii Outer Surface Protein A in Lyme Neuroborreliosis

et al. 2009

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We studied the T‐cell reactivity to overlapping peptides of B. garinii OspA, in order to locate possible immunodominant T‐cell epitopes in neuroborreliosis. Cells from cerebrospinal fluid (CSF) and blood from 39 patients with neuroborreliosis and 31 controls were stimulated with 31 overlapping peptides, and interferon‐γ secreting cells were detected by ELISPOT. The peptides OspA17–36, OspA49–68, OspA105–124, OspA137–156, OspA193–212 and OspA233–252 showed the highest frequency of positive responses, being positive in CSF from 38% to 50% of patients with neuroborreliosis. These peptides also elicited higher responses in CSF compared with controls (P = 0.004). CSF cells more often showed positive responses to these peptides than blood cells (P = 0.001), in line with a compartmentalization to the central nervous system. Thus, a set of potential T‐cell epitopes were identified in CSF cells from patients with neuroborreliosis. Further studies may reveal whether these epitopes can be used diagnostically and studies involving HLA interactions may show their possible pathogenetic importance.

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Section: Discussionsupporting

confidence: 81%

T‐Cell Epitope Mapping of the Borrelia garinii Outer Surface Protein A in Lyme Neuroborreliosis

et al. 2009

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“…In LM CSF, on the other hand, myeloid DC are abundant (up to 5000 cells/ml) [13], levels of IL-10 are relatively low, and IFN-g is present, augmenting production of IL-12 by myeloid DC. Such DC may interact with T cells intrathecally or in DCLN and induce new pools of Th1 cells, contributing to the strong and long-standing intrathecal Th1 response seen in Lyme neuroborreliosis [39]. Autoantigens such as myelin basic protein-like material (MBPLM) are released into the CSF during MS exacerbations [40].…”

Section: Discussionmentioning

confidence: 99%

Cerebrospinal fluid affects phenotype and functions of myeloid dendritic cells

Pashenkov

Soderstrom

Huang

et al. 2002

Clinical and Experimental Immunology

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SUMMARYMyeloid (CD11c + ) dendritic cells (DC) are present in cerebrospinal fluid (CSF), as well as in the meninges and choroid plexus. Functional studies of these DC are hindered or impossible. To obviate this problem, we investigated the effects of CSF supernatants from patients with non-inflammatory neurological diseases (NIND), multiple sclerosis (MS), bacterial meningitis (BM) and Lyme meningoencephalitis (LM) on immature monocyte-derived DC (moDC) from healthy donors. CSF supernatants caused maturation of moDC (MS > LM > NIND > BM), as reflected by a decrease in CD1a, and an increase in HLA-DR, CD80 and CD86 expression. The maturation effect of MS CSF and LM CSF could be blocked by anti-TNF-a MoAb or recombinant human IL-10. moDC cultured with BM CSF either remained immature or turned into CD14 + macrophage-like cells and were relatively inefficient at inducing T cell responses in vitro. In contrast, moDC cultured with LM CSF induced strong Th1 responses. Both BM CSF and LM CSF contained IFN-g, a cytokine that augments IL-12 production by moDC and hence should confer an ability to induce a Th1 response. However, BM CSF also contained high levels of IL-10, which could antagonize the effects of IFN-g on moDC. moDC cultured with MS CSF induced a higher production of IFN-g from T cells compared to moDC cultured with NIND CSF or BM CSF. In summary, soluble factors present in the CSF may influence the phenotype and functions of meningeal, choroid plexus and CSF DC which, in turn, may have an impact on the character of intrathecal T cell responses.

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“…The enzyme-linked immuno-spot (ELISPOT) was done as described previously [28] but slightly modified [29]. Sterile nitro-cellulose-bottomed 96-well microtitre plates (Multiscreen HA, Millipore, Bedford, Mass., USA) were coated with 15 mg/ml of mouse anti-human IFN-g 7B61 monoclonal antibody (mAB) or mouse anti-human IL-4 mAB (Mabtech AB, Stockholm, Sweden) overnight at 4 C. Nonspecific binding sites on the nitro-cellulose were blocked by incubation with Iscove's modification of Dulbeccos medium (Life Technologies, Täby, Sweden) supplemented with 50 U/ ml penicillin, 50 mg/ml streptomycin (Life Technologies), 10 ml/l 100´non-essential amino acids (Life Technologies) and 5 % FCS, for 30 min at 37 C.…”

Section: Methodsmentioning

confidence: 99%

Th1-like dominance in high-risk first-degree relatives of Type I diabetic patients

2000

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Compartmentalization of antigen specific cytokine responses to the central nervous system in CNS borreliosis: secretion of IFN-γ predominates over IL-4 secretion in response to outer surface proteins of Lyme disease Borrelia spirochetes

Cited by 62 publications

References 32 publications

T‐Cell Epitope Mapping of the Borrelia garinii Outer Surface Protein A in Lyme Neuroborreliosis

T‐Cell Epitope Mapping of the Borrelia garinii Outer Surface Protein A in Lyme Neuroborreliosis

Cerebrospinal fluid affects phenotype and functions of myeloid dendritic cells

Th1-like dominance in high-risk first-degree relatives of Type I diabetic patients

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