The Role of Unconventional T Cells in the Immune Response to the Gastric Pathogen Helicobacter pylori

Background: Helicobacter pylori infection is associated with development of chronic inflammation and infiltration of immune cells into the gastric mucosa. As unconventional T-lymphocytes expressing natural killer cell receptors are considered to play central roles in the immune response against infection, a study investigating their frequencies in normal and H. pylori-infected gastric mucosa was undertaken. Materials and Methods: Flow cytometry was used to quantify T-cells expressing the natural killer cell markers CD161, CD56, and CD94 in freshly isolated lymphocytes from the epithelial and lamina propria layers of gastric mucosa. Thirteen H. pylori-positive and 24 H. pylori-negative individuals were studied. Results: CD94 T-cells were the most abundant (up to 40%) natural killer receptor-positive T-cell population in epithelial and lamina propria layers of H. pylori-negative gastric mucosa. CD161 T-cells accounted for about one-third of all Tcells in both compartments, but the lowest proportion were of CD56 T-cells. Compared with H. pylori-negative mucosa, in H. pylori-infected mucosa the numbers of CD161 T-cells were significantly greater (p = 0.04) in the epithelium, whereas the numbers of CD56 T-cells were lower (p = 0.01) in the lamina propria. A minor population (< 2%) of Tcells in both mucosal layers of H. pylorinegative subjects were natural killer T-cells, and whose proportions were not significantly different (p > 0.05) to those in H. pylori-infected individuals. Conclusions: The predominance, heterogeneity, and distribution of natural killer cell receptor-positive T-cells at different locations within the gastric mucosa reflects a potential functional role during H. pylori infection and warrants further investigation. Innate immune cells, which include T-cell populations activated by glycolipids rather than peptides, are central to the outcome of the ensuing immune response but have not been studied in Helicobacter pylori infection [1]. Included in this cell population are Tcells that bear natural killer (NK) receptors, termed natural killer receptor-positive (NKR) T-cells. NKRT-cells become activated rapidly after stimulation, are capable of MHC -unrestricted cytotoxicity and can secrete large amounts of cytokines including interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), interleukin (IL)-2, and IL-4 [2–4]. Several NK receptors exist, including CD56, CD57, CD161, CD94, and the killer Ig-like receptors. Human NK receptors unlike T-cell receptors (TCRs) are not clonally distributed, antigenspecific receptors, but instead, they recognize HLA-A, -B, C, or -E molecules and deliver either inhibitory or activatory signals (reviewed in [5]). Moreover, some NK receptors function primarily as co-receptors amplifying the signal delivered through other receptors on the cell surface. Human CD56 T-cells display both NK-like and T-cell-restricted cytotoxicity in vitro [6] and exhibit potent cytokine secretion [4,7]. The NK marker CD161 is a costimulatory molecule that regulates the activity of CD1ddependent T-cells [8], whereas CD94 expression on T-cells is considered protective against viral infection and against the potential development of autoimmunity [9]. NKR + T-cells bearing the invariant TCR alpha chain, Vα24Jα18, are termed NKT-cells [10] and are recognized for their roles in regulating autoimmunity [11], as well as in defense against certain microbial infections [12]. These cells are