The Hyperresponsiveness of W/Wv Mice to Oral Sensitization Is Associated with a Decrease in TCR.GAMMA..DELTA.-T Cells

Abstract

The number of patients with food allergies has been increasing for various reasons (e.g., changes in diet, increased stress, etc.), but the mechanisms of the development and regulation of food allergy have not yet been fully elucidated. Thus, oral sensitization models in animals are important for better understanding the induction and regulation mechanisms of food allergy. [1][2][3] When the allergenicity of dietary proteins is evaluated in animal, it is desirable to perform the sensitization orally, preferably without using adjuvants. However, since orally administered food antigens induce tolerance by various mechanisms, [4][5][6] it is important to optimize the dosage of the allergen and the duration of immunization in order to achieve oral sensitization without inducing tolerance.In previous studies, we compared animal food allergy models using various strains of mice and rat, 7) and found that significant antigen-specific antibody production was successfully induced without any adjuvant by orally administering OVA for 9 weeks in B10A mice and BALB/c mice. More recently, W/W v mice have been proven to be a good responder to food allergens, because their antigen-specific antibody titer was much higher than in the other murine strains used. 8)It is important to clarify the cause of the high susceptibility of the W/W v mice to oral sensitization in order to elucidate the mechanism of development of food allergy.W/W v mice have mutations in the c-kit gene and exhibit defects or a deficiency of mast cells, red blood cells, and interstitial cells of Cajal, which ordinarily express c-kit protein.9,10) The c-kit protein is a member of the type III receptor tyrosine kinase family, and its dimer is a ligand for the stem cell factor (SCF).11) We have reported low susceptibility of the congenic wild-type (ϩ/ϩ) mice to oral sensitization. The lack of high sensitivity in c-kit-positive wild-type (ϩ/ϩ) mice suggested that the susceptibility of W/W v mice to oral sensitization is related to the mutations in the c-kit gene.12)The population of gd-IELs is much smaller in W/W v mice than in wild-type mice.12) Moreover, it has been demonstrated that the ratio of the gd-IELs to total T cells in mouse intestinal mucosa is much higher than in other peripheral lymphoid tissues, 13) and that gd-IELs have been found to develop thymus independently in cryptopatches (CPs), which are located in the lamina propria. CPs are the small clusters of immature lymphocytes (c-kitϩ, IL-7Rϩ, Thy-1ϩ, LFA-1ϩ).14,15) Thus, gd-IELs are thought to play an important role in immune responses in the mucosa, although their function in oral sensitization is not fully understood. 16)The objective of this study was to identify the cause of the high susceptibility of W/W v mice to oral sensitization, and we performed two experiments to achieve this objective. In the first experiment, congenic wild-type (ϩ/ϩ) mice were treated with the anti-TCRgd antibody before oral sensitization to OVA. In the second experiment, bone marrow cell-reconstituted W/W v mice with ...

Cocoa Diet and Antibody Immune Response in Preclinical Studies

“…It is worth noting that the cocoa diet increased the proportion of TCRγδ + and NK cells in three intestinal compartments (mesenteric lymph nodes, PP, and IEL), suggesting their role in the tolerogenic process. In line with this, unripe apple polyphenols induced an increase in the proportion of TCRγδ + IEL in association with the inhibition of the development of an oral sensitization model (25), and it was also reported that the reduction of TCRγδ + cells by the anti-TCRγβ antibody favors an oral sensitization in mice (120). Furthermore, NK cells could have regulatory functions contributing to the avoidance of sensitization in line with the reported prevention of allergic disease (121, 122).…”

Dietary unripe apple polyphenol inhibits the development of food allergies in murine models

“…Furthermore, we have shown that an additional decrease in the percentage of TCRγδ‐T cells in the IEL cells of the W/W V mice was also observed in the orally sensitized W/W V mice [15]. The proportion of TCRγδ‐T cells in the IEL of the W/W V mice reconstituted with bone marrow cells from C57BL/6J increased much more than that in the untreated W/W V mice and further extremely inhibited the development of oral sensitization [25]. These findings suggested that the lowering of the population of TCRγδ‐T cells in the IEL of the W/W V mice could be associated with the high oral sensitivity of the W/W V mice.…”

Effect of a cocoa diet on the small intestine and gut-associated lymphoid tissue composition in an oral sensitization model in rats

“…Our results are in line with those of Akiyama et al [35], who reported that unripe apple polyphenols inhibit oral sensitization associated with a rise in the proportion of TCRγδ+ IEL. In line with these studies, it was described that a decrease in the number of TCRγδ+ cells induced by anti-TCRγδ antibody treatment facilitated oral sensitization in mice [36].…”