Comparison of replication of adenovirus type 2 and type 4 in human lymphocyte cultures.

Adenovirus type 2 was capable of replicating in purified lymphocyte cultures from human adenoid specimens. Phytohemagglutinin stimulation enhanced the replication of virus. Viral titers of 103 to 104 50% tissue culture infective doses per ml were reached after 4 to 8 days. Only 1 to 3 per 106 cells were found to produce virus. In contrast, there was no evidence that lymphocyte cultures could support the replication of adenovirus type 4. The life span of cultures infected with type 2 or 4 was not reduced. The possibility that lymphocytes infected with virus play a role in initiating natural, persisting adenovirus infections of human adenoids is discussed.     

Activation of Human Lymphocyte Subpopulations by Mycoplasma pneumoniae

B- and T-cell-enriched preparations of lymphocytes from human blood (5 cases), adenoids (10 cases), and tonsils (4 cases) were examined for the in vitro stimulation response to Mycoplasma pneumoniae (MP). B lymphocytes did not respond to MP by DNA synthesis except for the B cells from one adenoid. T lymphocytes and nonfractionated lymphocytes from blood, from three of the adenoids and two of the tonsils showed a stimulation response to MP. Nonfractionated adenoid lymphocytes from altogether 22 children were examined, and a stimulation response to MP was demonstrated in 8 cases. Lymphocyte cultures from 11 adenoids and 2 tonsils were examined for MP-induced non-antigen-specific antibody production by a hemolytic plaque assay. In all these cultures MP activated production of antibody-secreting cells to sheep erythrocytes. It is concluded that MP can induce non-antigen-specific angibody production in human B lymphocytes without stimulating DNA synthesis in these cells. The proliferative response of adenoid, tonsil, and blood lymphocytes to MP is interpreted as an antigen-specific T-cell response.     

JCV/BKV and SV40 viral load in lymphoid tissues of young immunocompetent children from an area of North‐East Italy

Polyomavirus infection occurring during childhood is followed by a lifelong latency in immunocompetent subjects. The major site of polyomavirus persistence are the uroepithelial cells which leads to oral transmission. It has recently been hypothesized that tonsils could be a possible reservoir. The role of tonsil, adenoid, and peripheral blood mononuclear cells (PBMCs) as possible sites of JCV, BKV, and SV40 latency in young healthy children was assessed. Two hundred fifteen fresh specimens, including 57 tonsil, 80 adenoid, and 78 PBMC samples from 80 immunocompetent children (mean age 4.8 years) were analyzed to determine the viral load by quantitative real‐time PCR. The human herpes virus 6 (HHV‐6) was tested as a lymphotropic reference virus. Polyomavirus was detected in 5/80 (6.2%) children while HHV‐6 infection affected 27/80 children (33.7%) (P < 0.001). SV40 was detected in one adenoid sample, while footprints of BKV were found in one adenoid and three tonsil samples. JCV was never found in all samples. Polyomavirus sequences were not detected in the 78 blood samples. One adenoid and two tonsils from three children (1.4%) were positive for both polyomavirus and HHV‐6. Infections were characterized by low replication rates ranging typically from 1 × 10e²/5.5 × 10e⁴ to 6.8 × 10e³/8.5 × 10e⁴ viral copies/number of cells. In conclusion, tonsils and adenoids of children could effectively harbor BKV and SV40, although only very few cells proved to be infected. Nevertheless, the low prevalence of polyomavirus, in comparison with the lymphotropic HHV‐6, suggests that these tissues are unlikely to be the preferred site of polyomavirus latency, at least in younger children. J. Med. Virol. 82:1236–1240, 2010. © 2010 Wiley‐Liss, Inc.     

The adequacy of gross pathological examination of routine tonsils and adenoids in patients 21 years old and younger

Most hospitals microscopically examine all routine tonsil and adenoid specimens from healthy pediatric patients with recurrent infections or obstructive sleep apnea. Concern over missing the rare unsuspected, significant diagnosis propagates this practice. Careful gross examination for asymmetry and clinical findings should obviate the need for routine microscopic examination of tonsil and adenoid specimens in patients age 21 years and younger. A retrospective study was conducted using the SNOMED database of 4070 patients age 21 years or younger who underwent tonsillectomy and/or adenoidectomy between 1970 and July 2001 at the University of Florida. The age distribution of the study group was 0 to 5 years (52%), 6 to 12 years (37%), and 13 to 21 years (11%). Specimens consisted of tonsils only (15%), tonsils and adenoids (40%), and adenoids only (45%). Clinically significant diagnoses were diagnoses that impacted the care of patients and included malignancies and some infections. Non-clinically significant diagnoses included normal, acute or chronic tonsillitis, and tonsillar hyperplasia. Clinically significant pathological processes were seen in the tonsil or adenoid specimens of 3 of the 4070 patients. These 3 cases included a 2-year-old male with Burkitt's lymphoma, a 19-year-old male with non-Hodgkin's lymphoma (small noncleaved cell, non-Burkitt's type), and an 11-year-old male with a probable viral process but in whom a lymphoma could not be absolutely excluded. All 3 of these patients had signs and symptoms, including significant cervical lymphadenopathy, meriting microscopic analysis of the specimens. In conclusion, microscopic examination of all routine tonsils and adenoids for individuals 21 years or younger is not indicated. Gross examination is still recommended. Clinical suspicion and specimen asymmetry should be used to determine when thorough histological examination is merited.     

Identification and Immunolocalization of the Innate Immune Receptor CD14 in Hypertrophic Adenoids and Tonsils

The purpose of this study is to determine the expression of CD14 as a marker of the innate immunity in hypertrophic adenoids and tonsils. Twenty-four pediatric patients (age <12 years) with obstructive adenotonsillar hypertrophy, confirmed by sleep study were included in this study. Intensity and expression of positive CD14 infiltrating cells was assessed by immunohistochemistry in specific histologic areas. In tonsils, CD14 immunoreactivity was demonstrated in intraepithelial lymphocytes located in the basal layer of the stratified squamous mucoepithelium. CD14 expression was significantly higher in mucosal layers and inter-follicular areas of tonsils than adenoid tissues [(p < 0.001), (p = 0.021), respectively]. CD14 expression was significantly higher in the submucosal layers of adenoids than tonsil tissues (p = 0.002). Hypertrophic adenoids and tonsils from children with OSA are prominent sites of innate defense, with over expression of CD14. The enhanced expressions of CD14 cells in adenoids and tonsils may be an important factor for the development and persistence of adenoids and tonsils enlargement causing OSA in children. CD14 expression in adenoids and tonsils illustrates an important immunological sentinel function of the innate immunity of the upper airway.     

Identification and immunolocalization of the innate immune receptor CD14 in hypertrophic adenoids and tonsils

The purpose of this study is to determine the expression of CD14 as a marker of the innate immunity in hypertrophic adenoids and tonsils. Twenty-four pediatric patients (age <12 years) with obstructive adenotonsillar hypertrophy, confirmed by sleep study were included in this study. Intensity and expression of positive CD14 infiltrating cells was assessed by immunohistochemistry in specific histologic areas. In tonsils, CD14 immunoreactivity was demonstrated in intraepithelial lymphocytes located in the basal layer of the stratified squamous mucoepithelium. CD14 expression was significantly higher in mucosal layers and inter-follicular areas of tonsils than adenoid tissues [(p < 0.001), (p = 0.021), respectively]. CD14 expression was significantly higher in the submucosal layers of adenoids than tonsil tissues (p = 0.002). Hypertrophic adenoids and tonsils from children with OSA are prominent sites of innate defense, with over expression of CD14. The enhanced expressions of CD14 cells in adenoids and tonsils may be an important factor for the development and persistence of adenoids and tonsils enlargement causing OSA in children. CD14 expression in adenoids and tonsils illustrates an important immunological sentinel function of the innate immunity of the upper airway.     

Immunohistochemical characterization of intraepithelial and subepithelial mononuclear cells of the upper airways.

The upper airway is the first site of exposure to inhaled antigens and the site of initiation of mucosal immunity to certain antigens; however, the intraepithelial lymphoid populations of this region have not been well characterized. We studied 6-mu frozen tissue sections from tonsils, adenoids, and nasal mucosae using immunohistochemistry and a panel of antibodies to mononuclear antigens to determine whether nasal mucosa contained distinctive populations of mononuclear cells. Intraepithelial lymphocytes (IELs) of nasal mucosa were CD3+, CD8+, and mainly CD5+. Tonsil and adenoid both showed diffuse CD8+ IELs; clusters of CD4+ IELs were associated with B cells within the crypt epithelium. All nasal IELs were uniformly negative for Leu8 (homing receptor analog of Mel14). Scattered Leu8-positive cells were present within tonsil and adenoid crypt epithelium only. Nasal IELs rarely expressed HML1 and were often CD7-, whereas the majority of tonsillar and adenoidal IELs were HML1+ and variably CD7+. In nasal mucosa and in deep submucosa of tonsil and adenoid, 80 to 90% of T cell receptor expression was of alpha/beta type. There was a concentration of gamma/delta T cell receptor-positive cells in intraepithelial and subepithelial zones of tonsil and adenoid, with areas of up to 30% gamma/delta T cell receptor positivity. A population of intraepithelial dendritic cells was identified in all three tissues expressing mononuclear phagocyte system antigens CD14 and KiM1P, but lacking CD1a. Virtually no B cells and no organized subepithelial lymphoid tissue were identified in nasal mucosa. Nasal mucosal lymphoid tissue seems to differ from that of endodermally derived mucosae, tonsil, and adenoids to share similarities with both mucosa-associated lymphoid tissue and peripheral lymph nodes.     

Study of human T and B lymphocytes with heterologous antisera: IV. Subpopulations in tonsil and adenoid cell suspensions

Mononuclear cells from eighty-seven human tonsils and fourteen adenoids were examined for T and B cells and their subpopulations. Forty six percent of the tonsil cells were killed in the presence of C by an antiserum specific for T cells and 41.7% were able to form E rosettes. Among them 58% were `active'' E rosettes and 24% possessed Fc μ receptors as compared to 35 and 37%, respectively, in peripheral blood. Fifty percent of cells were detected by an antiserum recognizing B cells and monocytes; most of them bore surface immunoglobulins and complement receptors. None of the cells bound chicken erythrocytes coated with rabbit IgG. Only 1 to 3% of monocytes were detected by the peroxidase staining. Significant variations depending on the age of the donors were noticed: T cells increased from 42% in infants to 54.6% in adults whereas the B cells dropped from 56.2 to 38.5%. Similar distributions of cells were found in adenoids and tonsils of donors of the same age. About 2 to 3% of tonsil cells contained cytoplasmic immunoglobulins, more than one third of them being of the IgG class. The proliferative response of adenoid or tonsil cells to Con A, PWM and NWSM was similar to that of blood lymphocytes although their relative numbers of T and B cells were very different, whereas their response to PHA and ALG was slightly lower.     

Detection of adenovirus nucleic acid sequences in human tonsils in the absence of infectious virus

Human tonsillar and adenoid tissues from surgical specimens and cell cultures established therefrom were screened for adenovirus type 2 (Ad2) sequences by in situ hybridization. For labeling we have utilized biotinylated DNA probes. We report detection of adenoviral sequences after hybridization with adenovirus type 2 DNA probes in tissues as well as in cell cultures from specimens without any signs of infectious virus even after long-term cultivation. In the infected tonsils only some of the cells appear to carry viral sequences. In conclusion, truly latent adenovirus infections in man seem to occur.     

Active replication of HIV-1 at the lymphoepithelial surface of the tonsil.

Cells that are infected with HIV-1 were visualized at the mucosal surface of the nasopharyngeal and palatine tonsils in 14 specimens from patients with CD4+ T-cell counts of 200 to 900/microliter and 2- to 10-year histories of HIV-1 infection. Most of the cells with intracellular HIV-1 protein were small but multinucleated. The majority of these syncytia could be double labeled for HIV-1 RNA and a dendritic cell marker S100. In the palatine tonsil, the infected cells were not found in the stratified squamous epithelium that is adjacent to the pharynx. Instead, the S100+ infected syncytia were localized to the surface of tonsil invaginations or crypts. This mucosa, termed lymphoepithelium, contains antigen-transporting M cells that lie above regions where S100+ dendritic cells are juxtaposed with CD4+ lymphocytes. Likewise, infected cells were found in lymphoepithelium and not respiratory epithelium of nasopharyngeal tonsils or adenoids. We propose that lymphoepithelia, the histological term that describes the specialized regions where antigens access mucosa-associated lymphoid tissue, are sites where HIV-1 replication can be enhanced in syncytia derived from dendritic cells.     

Activation of Human T Lymphocytes by Soluble Protein A

The proliferative response of highly purified human peripheral blood or tonsil lymphocytes in the presence of soluble protein A (SpA) was investigated. SpA was shown to be a potent mitogen for T lymphocytes from peripheral blood or tonsils. Conversely, the non-T lymphocyte population from peripheral blood responded poorly to SpA, and SpA did not stimulate non-T lymphocytes from tonsils. The addition of mitomycin-treated T lymphocytes from peripheral blood enhanced the response of blood non-T lymphocytes to protein A. This effect was not found when non-T lymphocytes isolated from tonsils were cultured with mitomycin-treated T lymphocytes. The proliferative response of unseparated cells or purified lymphocyte populations was enhanced when adherent cells were added to the cultures. It is concluded that the soluble form of protein A activates mainly T lymphocytes and does not induce B lymphocyte proliferation.     

Antibody formation by human tonsil cells in vitro.

The ability of human tonsil lymphocytes to give an anti-SRBC response in conventional cultures and in microcultures was studied. It was found that about two-thirds of tonsils responded with a significant number of plaque-forming cells (PFC), and that in some instances the response could be augmented if allogeneic tonsil cell (irradiated or intact) were added. Moreover, tonsil lymphocytes which failed to give a response on their own often responded upon addition of an appropriate number of allogeneic tonsil cells. The response was remarkably improved if allogeneic tonsil supernatant or conditioned medium were added. An anti-SRBC response was also obtained if SRBC was omitted from the cultures. The frequency of anti-SRBC specific B cells was estimated as 1/60000 (f = 1-7 X 10(-5)).     

Structural and immunological characteristics of chronically inflamed adenotonsillar tissue in childhood

Recurrent or chronic adenotonsillar infections mainly affect children and frequently involve otherwise healthy subjects. Therefore, having excluded systemic immunological deficiencies, this disease may be due to a local dysfunction of the epithelial structures at either the rhino or oropharyngeal level. The aim of the present investigation was to analyze structural and immunological aspects of tonsils and adenoids in subjects who underwent adenotonsillectomy because of recurrent inflammatory episodes with fever. Histological studies and analyses of the cytokine patterns were carried out in palatine tonsils and adenoid samples from 105 patients who underwent adenoidectomy and bilateral extracapsular tonsillectomy for chronic inflammatory hypertrophy of these organs; 46 of the 105 cases examined presented hyperkeratosis of the crypt epithelium; in the remaining 59, the epithelium was hyperplastic with no signs of keratosis. Scanning electron microscopy revealed a continuous epithelial surface of polygon-shaped flattened cells with fissures towards the cryptic depressions. Titration of interleukin-1beta and tumor necrosis factor alpha in serum and tissues demonstrated higher concentrations in the adenotonsillar specimens, whereas the rise in interleukin-6 was more modest.     

Structural and Immunological Characteristics of Chronically Inflamed Adenotonsillar Tissue in Childhood

Recurrent or chronic adenotonsillar infections mainly affect children and frequently involve otherwise healthy subjects. Therefore, having excluded systemic immunological deficiencies, this disease may be due to a local dysfunction of the epithelial structures at either the rhino or oropharyngeal level. The aim of the present investigation was to analyze structural and immunological aspects of tonsils and adenoids in subjects who underwent adenotonsillectomy because of recurrent inflammatory episodes with fever. Histological studies and analyses of the cytokine patterns were carried out in palatine tonsils and adenoid samples from 105 patients who underwent adenoidectomy and bilateral extracapsular tonsillectomy for chronic inflammatory hypertrophy of these organs; 46 of the 105 cases examined presented hyperkeratosis of the crypt epithelium; in the remaining 59, the epithelium was hyperplastic with no signs of keratosis. Scanning electron microscopy revealed a continuous epithelial surface of polygon-shaped flattened cells with fissures towards the cryptic depressions. Titration of interleukin-1β and tumor necrosis factor alpha in serum and tissues demonstrated higher concentrations in the adenotonsillar specimens, whereas the rise in interleukin-6 was more modest.     

Secondary lymphoid tissue as an important site for WU polyomavirus infection in immunocompetent children

The polyomaviruses KI and WU (KIPyV and WUPyV) have been identified in respiratory specimens from children with acute respiratory infections, which suggests the respiratory tract as a possible site of infection. However, the persistence of infection in the lymphoid system is unknown. Fresh samples (n = 211) of tonsils, adenoids, and peripheral blood mononuclear cells (PBMCs) from 83 immunocompetent children (mean age 4.8 years) were tested for amplification of the KIPyV VP1 and WUPyV VP2 genes. The known BK and JC polyomaviruses and the lymphotropic human herpesvirus (HHV)-6 were also investigated by quantitative real-time PCR and direct sequencing. In addition, 98 nasopharyngeal swabs collected from children (mean age 6.2 years) affected by seasonal influenza-like illness were tested. Of the lymphoid tissues, 34.9% were positive for WUPyV, 4.8% for BK virus, and 33.8% for HHV-6. KIPyV and JC virus were not detected in these specimens. None of the polyomaviruses were detected in PBMCs. Among the nasopharyngeal samples, the prevalence of WUPyV was 27.5%, although 70% of the positive samples were co-infected with at least one of the following respiratory viruses: influenza virus, adenovirus, and respiratory syncytial virus. Phylogenetic analysis revealed high sequence homology (99%) between lymphoid- and nasopharynx-derived WUPyV strains. These results suggest that the tonsils and adenoids of immunocompetent children are a reservoir for WUPyV infection; probably due to the respiratory route of transmission. In addition, the prevalence of WUPyV was high among the children, and the virus was identified more frequently in older children than during the first years of life.     

Effect of allergic rhinitis on the expression of human β-defensin 2 in tonsils

BackgroundHuman β-defensins (HBDs) are a newly identified family of antimicrobial peptides that are expressed by epithelia on mucosal surfaces. Exposure of airway epithelial cells to T_H2-type cytokines results in a significant decrease in the antimicrobial activity of the cells.ObjectiveTo investigate the effect of allergic rhinitis on the expression of HBD-2 in tonsils and adenoids.MethodsPalatine tonsils and adenoids were obtained from 30 patients with no history of recurrent tonsillitis. The patients were divided into 2 groups: allergic rhinitis and nonallergic rhinitis groups. Real-time polymerase chain reaction analysis was used to measure messenger RNA (mRNA) levels of HBD-2 mRNA in tonsil and adenoid tissue samples from the 2 patient groups. Immunofluorescent staining and enzyme-linked immunosorbent assay (ELISA) were used to evaluate the expression of HBD-2 protein in tonsil and adenoid tissues. The concentration of the cytokines interleukin (IL) 4, IL-5, and interferon γ (IFN-γ) in tissue homogenates was measured by ELISA.ResultsImmunofluorescent staining data demonstrated the expression of HBD-2 protein in the surface epithelia of tonsils, and a marked difference in the staining intensity was observed the between 2 groups. HBD-2 mRNA and protein levels in the tonsils were significantly lower in the allergic rhinitis group than that in the nonallergic rhinitis group (P = .03 and P = .04, respectively). IL-5 and IFN-γ were not detected, and no significant difference was found in IL-4 concentrations in tonsil homogenates between the 2 groups.ConclusionAllergic rhinitis suppresses HBD-2, an epithelial antimicrobial peptide, in the tonsils.     

The Macrophage Origin of the HIV-Expressing Multinucleated Giant Cells in Hyperplastic Tonsils and Adenoids

Replication and storage of virus are characteristic features of hyperplastic lymphoid tissues in HIV infection. In opportunistic infections, HIV is synthesized by phagocytic mononuclear and Langhans'-type multinucleated macrophages that coexpress the dendritic cell-associated S-100 and p55 antigens. However, similar cells in hyperplastic tonsils and adenoids from HIV+ individuals were alternatively identified as macrophages or, on the basis of the same S-100 and p55 staining, as dendritic cells. To consider establishing the role of these HIV-rich cells in HIV disease, it is important to reconcile this apparent discrepancy in identity. Hyperplastic tonsils and adenoid specimens were analyzed by HIV RNA in situ hybridization (ISH), light and transmission electron microscopy (TEM), and immunohistochemistry (IHC) (HIV Gag p24 protein, S-100, p55, CD68, HAM56, lysozyme, alpha -1-anti-trypsin, and alpha -1-antichymotrypsin). In HIV+ pediatric and adult surgical specimens (n=11), the giant cells and their mononuclear counterpart were positive for both macrophage and p55 and S-100 IHC markers. In addition, TEM, p24 IHC, and ISH showed HIV expression by cells with typical features of macrophages. Furthermore, these cells were not unique to HIV+ specimens, being seen in 20% of hyperplastic T&A surgical specimens (n=57) lacking HIV as well as in several types of granulomatous processes, such as sarcoidosis. These cells appear to represent an activated phenotype that can develop independent of HIV, but that may represent a viral host in HIV-infected individuals. Thus, the giant and mononuclear cells that produce striking amounts of HIV in tonsils and adenoids are of macrophage origin, yet, as in opportunistic infections, share dendritic cell-associated antigens, reflecting a common CD34+ bone marrow progenitor.     

Interaction between 6/94 virus, a parainfluenza type 1 strain, and human leukocytes.

6/94 virus, a parainfluenza type 1 virus recovered by lysolecithin fusion of multiple sclerosis brain cell cultures with CV-1 cells, replicated in monocyte macrophages and lymphocytes from normal human donors and from a patient with multiple sclerosis. In macrophage cultures, hemadsorption-positive cells and high levels of infectious virus became apparent within 24 to 48 h after infection, persisted for 6 days, and then began to decrease. Phytohemagglutinin-stimulated macrophages yielded similar titers of virus, but the levels were maintained for a longer period of time. Macrophage-produced virus appeared to be infectious for other macrophages in the same culture. Both unstimulated and phytohemagglutinin-stimulated lymphocytes also supported virus replication. Significantly higher titers were produced in the stimulated cultures, T cell-enriched populations producing more virus than unseparated populations whether stimulated or unstimulated. The presence or absence of antibodies to the virus in the donors did not appear to influence the levels of virus obtained in any of the leukocyte cultures. However, an increase in blastic forms after 6/94 virus infection was noted in lymphocytes from donors with antibodies as revealed morphologically and by increased incorporations of tritiated thymidine. Furthermore, 6/94 virus-infected lymphocytes, unlike Sendai virus-infected lymphocytes, were able to respond well to mitogenic stimulation by phytohemagglutinin.     

Comparison of diploid fibroblast and rabbit kidney tissue cultures and a diploid fibroblast microtiter plate system for the isolation of herpes simplex virus.

We evaluated the relative sensitivities of two cell systems (rabbit kidney [RK] and human diploid fibroblast [DF; human embryonic tonsil]) in standard tube cultures versus DF cells in a 48-well microtiter plate system for the detection of both symptomatic and asymptomatic herpes simplex virus (HSV) infection. At least one system isolated HSV in 111 of 809 specimens (13.7%). HSV was isolated in RK tube cultures from 110 specimens (99%), in DF tube cultures from 91 specimens (82%), and in DF microtiter plates from 95 specimens (86%). The frequency of HSV isolation varied with the anatomic site and the presence or absence of a herpetic lesion. The sensitivities of the three culture systems remained similar whether the specimens were obtained from lesions or whether the specimens were taken to determine if asymptomatic excretion of HSV was present. While RK tube cultures were more sensitive than DF tube cultures, the DF microtiter plate system was as sensitive as DF tube cultures and its use is supported as a cheaper and less labor-intensive method for the detection of HSV.     

Human nasopharyngeal-associated lymphoreticular tissues. Functional analysis of subepithelial and intraepithelial B and T cells from adenoids and tonsils

Subepithelial and intraepithelial lymphocytes of human adenoids and tonsils were characterized and directly compared to determine the potential contribution of these tissues to mucosal and systemic immune responses. The distribution of T and B cell subsets, cytokine patterns, and antibody (Ab) isotype profiles were similar for adenoids and tonsils. Both tissues contained predominantly B cells ( approximately 65%), approximately 5% macrophages, and 30% CD3(+) T cells. The T cells were primarily of the CD4(+) subset ( approximately 80%). Tonsillar intraepithelial lymphocytes were also enriched in B cells. The analysis of dispersed cells revealed a higher frequency of cells secreting IgG than IgA and the predominant Ig subclass profiles were IgG1 > IgG3 and IgA1 > IgA2, respectively. In situ analysis also revealed higher numbers of IgG- than IgA-positive cells. These IgG-positive cells were present in the epithelium and in the subepithelial zones of both tonsils and adenoids. Mitogen-triggered T cells from tonsils and adenoids produced both Th1- and Th2-type cytokines, clearly exhibiting their pluripotentiality for support of cell-mediated and Ab responses. Interestingly, antigen-specific T cells produced interferon-gamma and lower levels of interleukin-5. These results suggest that adenoids and tonsils of the nasopharyngeal-associated lymphoreticular tissues represent a distinct component of the mucosal-associated lymphoreticular tissues with features of both systemic and mucosal compartments.