Monocyte‐derived dendritic cells can induce autoreactive CD4+ T cells showing myeloid lineage directed reactivity in healthy individuals

• Published in: European journal of immunology Vol. 45; no. 4; pp. 1030 - 1042
• Main Authors: Lam, Tin Sing, Meent, Marian, Falkenburg, JH Frederik, Jedema, Inge
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01-04-2015
• Subjects: Antigens; Autoantigens; Autoantigens - immunology; Autoimmunity - immunology; Autologous responses; Avidity; CD4 antigen; CD4+ T cells; CD4-Positive T-Lymphocytes - immunology; CD8 antigen; Cell Lineage - immunology; Cell Proliferation; Cells, Cultured; Clonal selection; Cytokines; Cytotoxicity; Dendritic cells; Dendritic Cells - immunology; Histocompatibility antigen HLA; HLA Antigens - immunology; Human behavior; Humans; Immune response; Immune system; Immunologic Memory - immunology; Immunological memory; Immunology; Lymphocyte Activation - immunology; Lymphocytes; Lymphocytes T; Memory cells; Monocytes; Myeloid cells; Myeloid Cells - immunology; Negative selection; Peripheral blood; Reactivity; Stimulation; T cell receptors; T-Lymphocytes, Cytotoxic - immunology; Thymus; Dendritic cells; Autologous responses; CD4+ T cells
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.201444819

T cells against self‐antigens can be detected in peripheral blood of healthy individuals, although intrathymic negative selection removes most high‐avidity T cells specific for self‐antigens from the peripheral repertoire. Moreover, spontaneous T‐cell proliferation following stimulation with autologous monocyte‐derived dendritic cells (autoDCs) has been observed in vitro. In this study, we characterized the nature and immunological basis of the autoDC reactivity in the T‐cell repertoire of healthy donors. We show that a minority of naive and memory CD4+ T cells within the healthy human T‐cell repertoire mediates HLA‐restricted reactivity against autoDCs, which behave like a normal antigen‐specific immune response. This reactivity appeared to be primarily directed against myeloid lineage cells. Although cytokine production by the reactive T cells was observed, this did not coincide with overt cytotoxic activity against autoDCs. AutoDC reactivity was also observed in the CD8+ T‐cell compartment, but this appeared to be mainly cytokine‐induced rather than antigen‐driven. In conclusion, we show that the presence of autoreactive T cells harboring the potential to react against autologous and HLA‐matched allogeneic myeloid cells is a common phenomenon in healthy individuals. These autoDC‐reactive T cells may help the induction of primary T‐cell responses at the DC priming site.