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Identification of human CD1d-restricted T-cell receptor (TCR)-invariant natural killer T (iNKT) cells has been dependent on utilizing combinations of monoclonal antibodies or CD1d tetramers, which do not allow for the most specific analysis of this T-cell subpopulation. A novel monoclonal antibody (clone 6B11), specific for the invariant CDR3 loop of human canonical Vα24Jα18 TCR α chain, was developed and used to specifically characterize iNKT cells. In healthy individuals studied for up to 1 year, a wide but stable frequency of circulating iNKT cells (range: 0·01–0·92%) was observed, with no differences in frequency by gender. Four stable iNKT cell subsets were characterized in peripheral blood based on the expression of CD4 and CD8, with CD8+ iNKT cells being a phenotypic and functionally different subset from CD4+ and double negative iNKT cells; in particular, LAG-3 was preferentially expressed on CD8+ iNKT cells. In addition, a strong negative linear correlation between the frequency of total iNKT cells and percentage of the CD4+ subset was observed. In terms of their potential association with disease, patients at risk for type 1 diabetes had significantly expanded frequencies of double negative iNKT cells when compared to matched controls and first-degree relatives. Moreover, peripheral blood CD4+ iNKT cells were the highest producers of interleukin-4, while the production of interferon-γ and tumour necrosis factor-α was similar amongst all iNKT cell subsets. These differences in iNKT cell subsets suggest that in humans the relative ratio of iNKT cell subsets may influence susceptibility vs. resistance to immune-mediated diseases. [ABSTRACT FROM AUTHOR]

CD1-restricted T cells have been shown to play a critical role in host defence, tumour surveillance, and maintenance of tolerance. However, immunologic outcomes resulting from activation of CD1d-restricted T cells can be either beneficial or deleterious. A major mechanism by which CD1d-restricted T cells are thought to exert immunoregulatory control is via effects on dendritic cell (DC) differentiation and migration. Important functional subsets of CD1d-restricted T cells are also known to exist and the potential implications for preferential subset activations are discussed. [ABSTRACT FROM AUTHOR]

Summary Human invariant natural killer (iNK) T cells expressing an invariant Vα24-Jα15 T-cell receptor (TCR) are thought to be important regulators of autoimmunity and tumour surveillance. Two major subsets of iNK T cells, CD4[sup +] or CD4[sup -] CD8[sup -] are known to exist, but the in vivo importance of CD4 expression is unclear. Since interleukin-12 (IL-12) is a key iNK T-cell-activating cytokine, the effect of IL-12 plus or minus the T-cell growth factor IL-2 on a large panel of CD4[sup +] versus CD4[sup -] CD8[sup -] iNK T-cell clones was examined. Strikingly, IL-12 and IL-2 significantly activated iNK T cells to secrete IL-4, interferon-γ and granulocyte–macrophage colony-stimulating factor, and up-regulated perforin expression in the absence of TCR stimulation. Furthermore, IL-2 and IL-12 treatment resulted in a preferential increase in apoptosis of CD4[sup -] CD8[sup -] clones. Thus, independent of TCR activation, IL-2 and IL-12 can directly activate iNK T cells and provide a selective advantage to the CD4[sup +] iNK T-cell population. [ABSTRACT FROM AUTHOR]

Invariant CD1D-restricted natural killer T (iNKT) cells function during innate and adaptive immunity and regulate numerous immune responses, such as autoimmune disease, tumour surveillance, infectious disease and abortions. However, the molecular basis of their functions and the nature of disease-associated defects of iNKT cells are unclear and have been the subject of recent controversy. Here, we review recent findings that underscore the potential importance of interactions between iNKT cells and dendritic cells (DCs) that indicate that iNKT cells regulate DC activity to shape both pro-inflammatory and tolerogenic immune responses. The ability to modulate iNKT-cell activity in vivo using the ligand a-galactosylceramide and to treat patients with autoimmune disease or cancer is evaluated also. [ABSTRACT FROM AUTHOR]

Investigates the presence of invariant CD1d-restricted natural killer T (iNKT) cells and their CD1d ligand at the human maternal-fetal interface. Characteristics of decidual iNKT cells; Demonstration of CD1d expression on fetal trophoblasts.

Presents a study where self and viral peptides can initiate lysis by autologous natural killer cells. Building of various peptides to HLA-Cw7 and HLA-Cw6; Cell lines and antibodies; Cytolytic assays; Computer modeling results.

Focuses on a study which demonstrated that natural killer cell activating receptor (NKAR) also enhances proliferation and killing of target cells by subsets of CD8+ ...B and CD8+ ... T cells, as well as by natural killer (NK) cells. Materials and methods used; Indepth look at NK cells and cytotoxic T cells; Results and discussion.