RESUMO
Among the CD1 proteins that present lipid antigens to T cells, CD1d is the only one that stimulates a population of T cells with an invariant T-cell receptor known as NKT cells. Sequencing of a 722 nucleotide gap in the dog (Canis lupus familiaris) genome revealed that the canine CD1D gene lacks a sequence homologous to exon 2 of human CD1D, coding for the start codon and signal peptide. Also, the canine CD1D gene contains three different short tandem repeats that disrupt the expected gene structure. Because canine CD1D cDNA lacks sequences homologous to human exon 2 and 3, the functionality of canine CD1d protein may be affected, and this could have consequences for the development and activation of canine NKT cells.
Assuntos
Antígenos CD1d/genética , Cães/genética , Sequências de Repetição em Tandem , Animais , DNA Complementar/genética , Éxons , Genoma , Células T Matadoras Naturais/metabolismo , Análise de Sequência de DNA , Homologia de Sequência , Transcrição GênicaRESUMO
To seek evidence for a role of molecular mimicry in the induction of Guillain-Barré syndrome (GBS), the authors studied Campylobacter jejuni-reactive T lymphocytes in patients with GBS. In contrast to controls, gammadelta T cells of patients with GBS with antecedent C jejuni infections failed to respond to C jejuni. Supplementing cell cultures with the cytokines interleukin-2 or interleukin-15 resulted in restoration of the gammadelta T cell proliferative response. Gammadelta T cell non-responsiveness may lead to defective regulation of antibody production, and in this way an (auto)immune response against ganglioside-like epitopes on peripheral nerve may cause GBS.
Assuntos
Infecções por Campylobacter/imunologia , Campylobacter jejuni/imunologia , Síndrome de Guillain-Barré/imunologia , Receptores de Antígenos de Linfócitos T gama-delta/imunologia , Linfócitos T/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Divisão Celular/efeitos dos fármacos , Divisão Celular/imunologia , Células Cultivadas , Feminino , Humanos , Técnicas Imunológicas , Interleucina-15/farmacologia , Interleucina-2/farmacologia , Masculino , Pessoa de Meia-Idade , Mimetismo Molecular/imunologia , Linfócitos T/citologia , Linfócitos T/efeitos dos fármacosRESUMO
Vasculitic neuropathy and chronic inflammatory demyelinating polyneuropathy (CIDP) are neuropathies characterized by a T-lymphocyte infiltrate in the peripheral nerves. The microenvironment in which these T cells become activated, and the molecules and cells that play a role in this process are incompletely understood. Using immunohistochemical analysis, we studied the effect of the presence of adhesion, costimulatory and antigen-presenting molecules on different cell types as a precondition for local T-cell activation in human sural nerve biopsies of seven patients with CIDP, three patients with vasculitic neuropathy and three healthy controls. In biopsies from CIDP and vasculitic neuropathy patients, but not in those from healthy controls, Schwann cells expressed the adhesion/T-cell stimulatory molecule CD58 (LFA-3). The CD58 molecule was also present on endothelial cells of all vasculitic neuropathy patients and one CIDP patient. In biopsies from normal controls and patients, CD54 (ICAM-1) expression was detectable on microvascular endothelial cells. In addition, expression of the costimulatory molecule CD86 was detected on vascular tissue in patients with vasculitic neuropathy. Although macrophages were always present in all subjects, expression of the major histocompatibility complex (MHC)-like molecule CD1a by macrophages was restricted to biopsies from two CIDP patients and one vasculitic neuropathy patient. Unexpectedly, Schwann cells of a single vasculitis patient strongly expressed CD1b, a molecule involved in the presentation of self-glycolipids to T cells. Schwann cells in biopsies from patients and normal controls expressed high levels of the invariant chain, CD74, a molecule involved in the intracellular sorting of MHC class II molecules. There was no evidence for the presence of dendritic cells in sural nerve biopsies. These findings support a model in which T-cell activation can be initiated and/or perpetuated locally in sural nerve biopsies of patients with CIDP and vasculitic neuropathy, and predict an important role for Schwann cells and endothelial cells.