Immune cells of the human peripheral taste system: dominant dendritic cells and CD4 T cells

Abstract

Taste loss or alterations can seriously impact health and quality of life due to the resulting negative influence on eating habits and nutrition. Infection and inflammation are thought to be some of the most common causes of taste perception disorders. Supporting this view, neuro-immune interactions in the peripheral gustatory system have been identified, underlying the importance of this tissue in mucosal immunity, but we have little understanding of how these interactions influence taste perception directly or indirectly. This limited understanding is evident by the lack of even a basic knowledge of the resident immune cell populations in or near taste tissues. The present study characterized the distribution and population of the major immune cells and their subsets in healthy human anterior, lingual, fungiform papillae (FP) using immunohistochemistry. Dendritic cells (DCs) were the predominant innate immune cells in this tissue, including four subtypes: CD11c(+) DCs, DC-SIGN+ immature DCs, CD83(+) mature DCs, and CD1a(+) DCs (Langerhans cells). While most DCs were localized beneath the lamina propria and only moderately in the epithelium, CD1a(+) Langerhans cells were exclusively present within the epithelium and not in sub-strata. A small number of macrophages were observed. T lymphocytes were present throughout the FP with CD4(+) T cells more prevalent than CD8(+) T cells. Very few CD19(+) B lymphocytes were detected. The results show that DCs, macrophages, and T lymphocytes are the constitutive guardians of human FP taste tissue, with DCs and CD4 T cells being dominant, while B lymphocytes are rare under normal, healthy conditions. These observations provide a basic anatomical foundation for the immune response in the healthy human tongue as a basis for subsequent disease-related studies, but none of the present data indicate that the immune cell populations identified are, in fact, altered in individuals with abnormal taste perception.

Figure 1

Quantitative analysis of specific cells in fungiform papillae. A. Specifically stained cells (brown) in fungiform papillae; B, Total area of epithelium (the area within the green line) and area of stained cells (red) in epithelium selected by using computer-assisted image analysis. C. Total area of lamina propria and area of stained cells in lamina propria.

Figure 2

Tissue structure of fungiform papillae. A. Showing the keratinized, stratified epithelium and underlying lamina propria. Note the taste buds embedded in epithelium (dotted line), epithelium ridges (ER) extending to connective tissue, small blood vessels (BV) and various types of cells. HE, 10 ×10 magnification; B. Antibody ik67 labeled proliferative cells of basal layer of epithelium. 10 × 20 magnification.

Figure 3

MHC class II expression in fungiform papillae. A. Negative control performed by skipping primary antibody; B. MHC class II expression and distribution. Frozen sections of human fungiform papillae were labeled with mouse against human HLA DR antibody. Note that the molecules present in intraepithelial and subepithelial cells but not in epithelial cells. 10 × 20 magnification.

Figure 4

Dendritic cells in fungiform papillae. A. CD11c staining dendritic cells; B. DC-SIGN staining immature dendritic cells; C. CD83 staining mature dendritic cells, and D. CD1a staining Langerhans cells. Note the difference in distributions of CD1a Langerhans cells, which are mainly present in epithelium, and CD11c dendritic cells, which are distributed both in epithelial and connective compartments. 10 × 20 magnification.

Figure 5

CD64+ macrophages in fungiform papillae. A. Macrophages were mainly distributed in the lamina propria, 10 × 20 magnification; B. High magnification of image showing macrophages occasionally migrate through the basement membrane into the epithelium. 10 × 60 magnification.

Figure 6

Lymphocytes in fungiform papillae. A. CD4 helper T cells; B. CD8 cytotoxic T cells; C. Showing no CD19 staining B lymphocytes. 10 × 20 magnification.