Class I-Restricted T Cell-Associated Molecule Is a Marker for IFN-γ-Producing iNKT Cells in Healthy Subjects and Patients with Type 1 Diabetes

Abstract

Class I-restricted T cell-associated molecule (CRTAM) is an activation marker expressed on the cell surface of activated invariant natural killer T (iNKT) cells, CD8 T cells, and a small subset of CD4 T cells. CRTAM has also been associated with a proinflammatory profile in murine CD4 T cells. However, CRTAM has not been thoroughly explored in human cells. This work focused on evaluating CRTAM expression in human iNKT lymphocytes after activation with α-galactosylceramide, its widely used specific glycolipid antigen. We also analyzed the involvement of costimulatory molecules in CRTAM expression and whether CRTAM expression is associated with a specific effector cytokine profile. We found that the signal produced by invariant T cell receptor (iTCR) engagement with α-galactosylceramide is sufficient to trigger CRTAM expression on human iNKT cells after 18 h of stimulation. Moreover, we observed a clear association between CRTAM expression and IFN-γ production in iNKT cells from healthy subjects and patients with type 1 diabetes. However, blocking the engagement of costimulatory molecules, such as CD40, CD80, and CD86, did not modify CRTAM expression. These results indicate that CRTAM may also play a role in triggering the production of IFN-γ in human iNKT cells and that CRTAM could be used as a marker to identify these inflammatory cells.

Detection and quantification of T-cell subpopulations and NK cells in peripheral blood from healthy individuals

“…The expression of these molecules in humans and mice occurs exclusively in activated T cells. [7][8][9] In the case of the chemokine receptor CCR7 (associated with the T lymphocytes retention in lymphoid organs), a low to no expression in activated T cells was reported. 10 However, it has been found that CD8+ T cells, after being activated by a specific antigen model (meaning, a monoclonal activation), express CCR7.…”

Determinación y cuantificación de subpoblaciones de linfocitos T y células natural killer en sangre periférica de individuos sanos por citometría de flujo

“…Estas dos moléculas tienen un patrón de expresión similar: aproximadamente de 16 a 18 horas postactivación se alcanza el máximo nivel de expresión y es de carácter transitorio (es decir, las células dejan de expresar las moléculas después de cierto tiempo), por lo que se refieren como marcadores de activación temprana. La expresión de esta molécula en humanos y ratones se presenta exclusivamente en linfocitos T activados [7][8][9] . En el caso del receptor de quimiocina CCR7 (asociado con la retención de los linfocitos T en órganos linfoides), se ha reportado de baja a nula expresión en los linfocitos T activados, principalmente 10 .…”

Natural killer T Cells: A Powerful Via in the Regulation of Non Communicable Chronic Diseases

“…In non-obese diabetic mice (NOD) that developed type 1 diabetes, progressive destruction of insulin-producing β cells was found with mononuclear cell infiltration. In many studies, it has been identified an infiltration of Th1-type cytokine-producing cells that cause destructive insulitis [9,[12][13][14]. A decrease in the number of V14i NKT cells has been found in the NOD mice thymus, spleen, bone marrow and liver.…”

“…A decrease in V24+ CD4-CD8-(double negative-DN) cells in peripheral blood has been reported in humans with type 1 diabetes, compared to twins and triplets without diabetes. Our working group demonstrated that the CRTAM molecule favours the production of IFN-in peripheral blood invariant NKT (iNKT) cells of patients with type 1 diabetes [9]. There is also an alteration in the production of IL-4 by V24 NKT cells as in NOD mice [23].…”

“…In humans they express the α homologue chain Vα24Jα18 [8], as well as the chain Vβ11, NKR-P1A (CD161), CD122, CD56, CD57 and other molecules such as CD44 high, CD45RB low, CD62L high, indicators of an activation/memory phenotype, and CD69, early activation marker, CD28+, CD49d/e/f, chemokine receptors such as CCR2, CCR5, CXCR3, CXCR4, CCR6, CXCR6 ( Figure 1). In recent years, it has also been found the expression of the CRTAM molecule in both species, once they have been activated by mitogens [5,9].…”