RESUMO
Cytotoxic T cells play an important role in graft-versus-host-disease (GvHD) and graft-versus-leukaemia/myeloma, which may occur in patients treated with an allogeneic stem cell transplantation (ASCT). Here, we describe the selection of a myeloma reactive CD4+ cytotoxic T cell-line (CTL) and two CD4+ clones from this CTL. The CTL was generated from the blood from a patient with multiple myeloma (MM) with graft versus myeloma/GvHD, following an ASCT. The CTL was stimulated using irradiated peripheral blood mononuclear cells and EBV transformed B cells from the myeloma patient (EBVp), both of which were obtained prior to ASCT. Both the CTL and the two T cell clones specifically lysed EBVp and secreted IFN-gamma after coculture with EBVp and autologous myeloma tumour cells in a class II restricted fashion. These results show that myeloma tumour cells and autologous B cells present a common polymorphic peptide that functions as a target for graft derived cytotoxic T cells. Identification of these proteins will give insight into the relationship between graft versus myeloma (GvM) and GvHD and may provide immunotherapeutical targets in the treatment of MM.
Assuntos
Linfócitos B/imunologia , Reação Enxerto-Hospedeiro/imunologia , Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo/imunologia , Plasmócitos/imunologia , Antígenos de Superfície/análise , Linfócitos T CD4-Positivos/imunologia , Linhagem Celular , Transformação Celular Viral , Herpesvirus Humano 4 , Humanos , Interferon gama/metabolismo , Ativação Linfocitária/imunologia , Masculino , Pessoa de Meia-IdadeRESUMO
Vbeta usage of muscle-infiltrating T lymphocytes in polymyositis (PM) and sporadic inclusion body myositis (s-IBM) was correlated with clinical and histopathological features. Immunohistochemical analysis was combined with complementarity-determining region 3 (CDR3) length analysis in nine muscle biopsies of eight PM patients and six biopsies of five s-IBM patients. Vbeta usage was heterogeneous in seven patients. Four of these patients had definite PM with endomysial located T cell infiltrates, but T cells specifically surrounding and invading individual non-necrotic fibers were not found. In two s-IBM patients, Vbeta 2 usage was increased. In one of them, a repeat biopsy showed a heterogeneous Vbeta usage. We conclude that clonal expansion of muscle-infiltrating T cells could only be detected in part of the patients. Explanations may be that clonal expansion does not take place in all disease phases and that PM is a heterogeneous disease with respect to pathogenesis.