CD8+ T Lymphocyte and NK Cell Network: Circuitry in the Cytotoxic Domain of Immunity

Abstract

Multiple effector layers in the immune system ensure an optimal temporal and spatial distribution of immune defense. Cytotoxic innate lymphoid natural killers (NK) and adaptive CD8 + T lymphocytes (CTL) interact to elicit specific cytolytic outcomes. The CTL carry antigen-specific T cell receptors (TCR) to recognize cognate peptides bound with major histocompatibility complex class-I (MHC-I) or human leukocyte antigen (HLA) molecules on target cells. Upon TCR engagement with MHC-I:peptide at a threshold of avidity, T cell intracellular programs converge into cytolytic activity. By contrast, NK cells lack antigen-specific receptors but express a repertoire of highly polymorphic and polygenic inhibitory and activating receptors that bind various ligands including MHC and like molecules. A highly calibrated maturation enables NK cells to eliminate target cells with lowered or absent MHC-I or induced MHC-I-related molecules while maintaining their tolerance toward self-MHC. Both CTL and mature NK cells undergo membranous reorganization and express various effector molecules to eliminate aberrant cells undergoing a stress of transformation, infection or other pathological noxa. Here, we present the cellular modules that underlie the CTL–NK circuitry to maximize their effector cooperativity against stressed or cancerous cells.

Cytotoxic lymphocytes are dysregulated in multisystem inflammatory syndrome in children

“…While these cell types share transcriptional signatures, our results suggest both independently contribute to disease. The predominant cytotoxic cells of the immune system, CD8 + T-cells and NK cells are equipped to kill infected or otherwise compromised cells and operate in synchrony, interacting directly and indirectly to co-regulate one another( Uzhachenko and Shanker, 2019 ). NK cell depletion is known to prevent CD8 + T-cell exhaustion( Cook and Whitmire, 2013 ; Waggoner et al, 2011 ), and the absence of NK-dependent clonal expansion of CD8 + T-cell exhaustion after viral infection can lead to severe and even fatal T-cell immunopathology( Cook and Whitmire, 2013 ; Waggoner et al, 2011 ).…”

Single-cell transcriptome atlas of lung adenocarcinoma featured with ground glass nodules

“…Upon activation, CD8+ T cells differentiate into cytotoxic T cells (CTLs), which is the major functional subpopulation. CTL can specifically recognize endogenous antigenic peptides presented by the major histocompatibility complex I, thereby killing tumor cells 26 . We conducted the GSVA analyses to compare the differences of pathways between the GGN-ADC-derived and SADC-derived CD8+ T cells (Fig.…”

Immune Characterization of Ovarian Cancer Reveals New Cell Subtypes With Different Prognoses, Immune Risks, and Molecular Mechanisms

“…To analyze the immune landscape of OV, consistent clustering was used to divide OV samples on the basis of the proportion of the 23 TME cell types. As a result, four new cell subtypes of OV were identified and named according to the functions of the cells: the immune procancer cell subtype (IPCCS, n = 52) ( Kalluri and Zeisberg, 2006 ; Yuan et al, 2017 ; Lee et al, 2019 ), immune killer cell subtype (IKCS, n = 62) ( Uzhachenko and Shanker, 2019 ), immune proantibody cell subtype (IPACS, n = 24) ( Oracki et al, 2010 ), and immune helper cell subtype (IHCS, n = 34) ( Banchereau and Steinman, 1998 ; Crotty, 2019 ; Figure 1A and Supplementary Table S2 ). The OS analysis indicated that IPCCS was associated with the poorest prognosis, and the other three subtypes were associated with similar or better prognosis than IPCCS ( P < 0.001, Figure 1B ).…”