CD4 and CD8 co-receptors are co-expressed on a large number of thymic T cells during development but such CD4+CD8+ double-positive double-positive (DP) T cells are much rare in the peripheral. For a long time, peripheral mature T cells were thought to express CD4 or CD8 in a mutually exclusive manner. With the identification of CD4+CD8+ intraepithelial T lymphocytes abundantly in the intestine and the reports of other CD4+CD8+ DP T cells in circulation or non-lymphoid organs, a heterogeneous pool of CD4+CD8+ DP T cells emerges but their phenotype and function remain unclear and sometimes controversial. We analysed human intestinal T cells by scRNA-seq and identified phenotypically distinct CD4+CD8+ DP T cells including two distinct CD4+CD8αα+ T cell subsets and other CD4+CD8αβ+ T cell subsets closely related to regulator T (Treg) cells, follicular helper T (Tfh) cells, GZMK+ CD8+ T cells, CD161+ CD8+ T cells and proliferating CD8+ γδ T, suggesting a broad spectrum of CD4+CD8+ DP T cells than previously appreciated. We found CD8+ Treg cells were highly induced by immune checkpoint inhibitor therapies and particularly associated with the development of colitis, which might be driven by pro-inflammatory cytokines in particular IFNγ. Single-cell landscape of CD4+CD8+ DP T cells not only advances the current understanding the heterogeneity of their phenotypes and functions but also discovers potential biomarkers for response and adverse events to immunotherapy.