Monocyte-derived dendritic cells can induce autoreactive CD4 super(+) 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: 01-04-2015
• 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 super(+) 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 super(+) 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.