Investigating immune tolerance: characterization of immunoregulatory DN T cells

• Published in: The Journal of immunology (1950) 2022-05, Vol.208 (1_Supplement), p.44-44.15
• Main Authors: Pasquin, Sarah, Pelletier, Adam-Nicolas, Lombard-Vadnais, Félix, Chabot-Roy, Geneviève, Collin, Roxanne, Coderre, Lise, Lesage, Sylvie
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.208.Supp.44.15

Autoimmunity results from defects in immune tolerance pathways that impair the capacity of immune cells to distinguish between self and non-self. One of these immune tolerance processes involves immunoregulatory TCRαβ+CD4−CD8− double negative T cells (DN T). Indeed, DN T cells protect from autoimmune pathologies and graft rejection in mice. Similarly, high DN T cell numbers correlate with a low incidence of chronic graft-versus-host disease in humans, an autoimmune-like pathology. While the thymic differentiation process of DN T cells was recently described, the function of these unconventional T cells is still poorly documented. To characterize DN T cells, we performed bulk RNA sequencing on CD4, CD8, γδ and DN T cells isolated from mouse spleen. Comparison of the transcriptome profiles revealed that DN T cells express a unique signature. Moreover, following in vitro stimulation, we find that DN T cells also present a distinct cytokine secretion pattern. Interestingly, we observed a lower induction of CD69, LAG-3 and PD-1 on DN T cells in comparison to CD4 and CD8 T cells, whereas LCK phosphorylation is unabated. DN T cell proliferation in mixed lymphocyte reactions is also lower than that of CD4 and CD8 T cells. Overall, our transcriptomic and cytokine analyses clearly identify DN T cells as a unique T cell subset. Moreover, while DN T cells do not express an exhaustion profile, they are more refractory to in vitro T cell stimulation than conventional T cells. A better characterization of DN T cell function will help conceive novel immunotherapies to treat autoimmune diseases. Supported by the Canadian Institutes of Health Research - PJT 159603. S.P. was supported by a postdoctoral CIHR fellowship