Low dose endoluminal photodynamic therapy improves murine T cell-mediated colitis.

BACKGROUND AND STUDY AIMS: Low dose photodynamic therapy (LDPDT) may modify the mucosal immune response and may thus provide a therapy for Crohn's disease. We evaluated the efficacy and safety of this technique in a murine T cell-mediated colitis model. METHODS: The safety of LDPDT was first tested in BALB/c mice. Naïve T cells were used to induce colitis in mice with severe combined immunodeficiency, which were followed up endoscopically, and a murine endoscopic index of colitis (MEIC) was developed. The efficacy of LDPDT (10 J/cm (2); delta-aminolevulinic acid, 15 mg/kg bodyweight) was then tested on mice with moderate colitis, while a disease control group received no treatment. The MEIC, weight, length, and histology of the colon, cytokine expression indices, number of mucosal CD4 (+) T cells, percentage of apoptotic CD4 (+) T cells, body weight, and systemic side effects were evaluated. RESULTS: LDPDT improved the MEIC ( P = 0.011) and the histological score ( P = 0.025), diminished the expression indices of the proinflammatory cytokines, interleukin-6 ( P = 0.042), interleukin-17 ( P = 0.029), and interferon-gamma ( P = 0.014), decreased the number of mucosal CD4 (+) T cells, and increased the percentage of apoptotic CD4 (+) T cells compared with the disease control group. No local or systemic side effects occurred. CONCLUSION: LDPDT improves murine T cell-mediated colitis, decreases the proinflammatory cytokines interleukin-6, interleukin-17, and interferon-gamma, and decreases the number of CD4 (+) T cells. No adverse events were observed. Therefore, this technique is now being evaluated in patients with inflammatory bowel disease.

A case of Muir-Torre syndrome associated with mucinous hepatic cholangiocarcinoma and a novel germline mutation of the MSH2 gene.

Muir-Torre syndrome (MTS) is a rare cancer-predisposing syndrome that is autosomal dominantly inherited and characterized by the development of sebaceous skin lesions (adenomas, epitheliomas, basaliomas and carcinomas). These lesions are typically associated with tumors that belong to the spectrum of hereditary nonpolyposis colorectal cancer (HNPCC) (i.e., tumors of the colorectum, endometrium, stomach or ovary). Biliary malignancy in association with MTS has only rarely been reported. We report a case of Muir-Torre syndrome associated with intrahepatic cholangiocarcinoma, a location not previously described, and associated with a novel missense mutation of the MSH2 gene (c.2026T > C), predicted to disrupt the function of the gene.

IL-22-induced antimicrobial peptides are key determinants of mucosal vaccine-induced protection against H. pylori in mice.

Despite the recent description of the mucosal vaccine-induced reduction of Helicobacter pylori natural infection in a phase 3 clinical trial, the absence of immune correlates of protection slows the final development of the vaccine. In this study, we evaluated the role of interleukin (IL)-22 in mucosal vaccine-induced protection. Gastric IL-22 levels were increased in mice intranasally immunized with urease+cholera toxin and challenged with H. felis, as compared with controls. Flow cytometry analysis showed that a peak of CD4+IL-22+IL-17+ T cells infiltrating the gastric mucosa occurred in immunized mice in contrast to control mice. The inhibition of the IL-22 biological activity prevented the vaccine-induced reduction of H. pylori infection. Remarkably, anti-microbial peptides (AMPs) extracted from the stomachs of vaccinated mice, but not from the stomachs of non-immunized or immunized mice, injected with anti-IL-22 antibodies efficiently killed H. pylori in vitro. Finally, H. pylori infection in vaccinated RegIIIß-deficient mice was not reduced as efficiently as in wild-type mice. These results demonstrate that IL-22 has a critical role in vaccine-induced protection, by promoting the expression of AMPs, such as RegIIIß, capable of killing Helicobacter. Therefore, it can be concluded that urease-specific memory Th17/Th22 cells could constitute immune correlates of vaccine protection in humans.

Digital image DNA cytometry: a useful tool for the evaluation of malignancy in biliary strictures.

BACKGROUND: Cytologic evaluation of the biliary tract strictures is nowadays widely used for distinguishing between benign and malignant lesions but remains a challenge for some problematic cases. Digital Image cytometry (DNA-cytometry) helps cytopathologists to resolve some unclear situations. METHODS: We have analysed 41 specimens of bile duct brushings obtained from patients during ERCP (11 benign cases, 7 suspicious for malignancy cases and 23 malignant cases) by DNA-cytometry and correlated them with the histological biopsy counterpart. RESULTS: All eleven cytological and histological benign cases were DNA-diploid and among 22 patients with malignant cytological and histological diagnosis 21 were DNA-aneuploid. One case considered malignant by the cytopathologist revealed DNA-aneuploid but malignancy could not be confirmed by histology. The analysis of the suspicious for malignancy cases revealed that all DNA-aneuploid cases were malignant and all DNA-diploid cases were benign referring to the follow-up of the patients. The comparison between cytology alone and cytology combined with DNA-cytometry related to the histological diagnosis (gold standard) resulted in a sensitivity of 100% and a specificity of 79% for cytology alone; a specificity of 94% and a sensitivity 92% for DNA-cytometry and a specificity of 93% and a sensitivity of 100% with combined analyses. The positive predictive value was 90% for cytology, 96% for DNA-cytometry and for both analyses. The negative predictive value showed 100% for cytology, 89% for DNA-cytometry and 100% for combined studies. CONCLUSIONS: Despite the limited number of patients involved in the study, the results obtained indicate an increased of specificity and of positive predictive value using DNA-cytometry. These results confirm the pertinence of these method for challenging cases, in conjunction with other available diagnostic tools.

Irinotecan-induced colitis.

Irinotecan (CPT-11) is a chemotherapeutic drug used to treat tumors by acting on malignant cells through inhibition of DNA topoisomerase I and inducing premature apoptosis. Major toxic effects of Irinotecan are myelosuppression and gastrointestinal (GI) toxicity, which limits the dose of administration, particularly severe diarrhea with a delay of onset. However, according to the literature, serious GI side effects are uncommon, comprising 3% of the reported cases. The mechanism of Irinotecan-induced delayed diarrhea is unknown and unpredictable. To our knowledge, this is the first case of colitis associated with Irinotecan administration for temporal glioblastoma documented by biopsies. The histopathologic findings are described and the potential mechanisms inducing such lesions are discussed.

p53 and Ki-ras as prognostic factors for Dukes' stage B colorectal cancer.

Mutations of the TP53 and Ki-ras genes have been reported to be of prognostic importance in colorectal carcinomas. An increased intracellular concentration of the p53 protein, although not identical to, is sometimes seen in tumours with TP53 mutation and has been correlated with poor prognosis in some tumour types. Previous colorectal cancer studies, addressing the prognostic importance of Ki-ras mutation and TP53 aberrations, yielded contradictory results. The aim of this study was to determine in a clinically and therapeutically homogeneous group of 122 sporadic Dukes' B colorectal carcinomas with a median follow-up of 67 months (3-144 months) whether or not p53 protein expression, TP53 mutation and K-ras mutation correlated with prognosis. p53 staining was performed by immunohistochemistry, using the monoclonal antibody DO7 on paraffin-embedded tissue. Mutations in exons 5-8 of the TP53 gene and in codons 12 and 13 of the K-ras gene were assayed in paraffin-embedded tissue by the single-strand conformation polymorphism (SSCP) assay. Nuclear p53 staining was found in 57 (47%) tumours. Aberrant migration patterns indicating mutation of the TP53 gene were found in 39 (32%) tumours. Forty-six carcinomas (38%) showed a mutation of the Ki-ras codons 12 or 13. In a univariate analysis, patients with wild-type TP53 status showed a trend towards better survival, compared with those with mutated TP53 (log-rank test, P = 0.051). Likewise, tumours immunohistochemically positive for p53 showed a worse prognosis than p53-negative tumours (P = 0.010). The presence or absence of mutations in Ki-ras did not correlate with prognosis (P = 0.703). In multivariate analysis, only p53 immunoreactivity emerged as an independent marker for prognosis hazard ratio (HR) = 2.16, 95% confidence interval (CI) 1.12-4.11, P = 0.02). Assessment of p53 protein expression is more discriminative than TP53 mutation to predict the outcome of Dukes' stage B tumours and could be a useful tool to identify patients who might benefit from adjuvant therapy.

The effects of omeprazole on healing and appearance of small gastric and duodenal lesions during dosing with diclofenac in healthy subjects.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are associated with gastrointestinal mucosal damage. Omeprazole prevents the formation, and accelerates the healing, of NSAID-induced ulcers. AIM: To test whether omeprazole accelerates healing of standardized gastroduodenal lesions in the presence of diclofenac. METHODS: In a double-blind, double-dummy, placebo-controlled, crossover study, 12 healthy volunteers received consecutive, 2-week courses of omeprazole (40 mg o.d.) and placebo, in random order, with an intervening, 4-week washout period; diclofenac (50 mg t.d.s.), was given for the second week of each course. Five endoscopies were performed, one at the outset and the others before and after each course of diclofenac. Biopsies were taken from the endoscopically normal mucosa of the corpus, antrum and duodenum and also from any new mucosal lesion that developed after diclofenac. The sites of biopsies taken before each course of diclofenac were evaluated endoscopically after each course to assess the extent of healing according to a predetermined healing score scale. RESULTS: The healing scores observed after administration of placebo/diclofenac (median=0; range 0-6) and after omeprazole/diclofenac (median=0; range 0-6; P=0.17) did not differ. Small gastroduodenal lesions developed de novo in six subjects during placebo/diclofenac and in seven during omeprazole/diclofenac. Focal chemical gastropathy was observed only in close proximity to macroscopic lesions. CONCLUSIONS: In healthy subjects, omeprazole does not accelerate the healing of pre-existing mucosal lesions or prevent the development of small diclofenac-induced mucosal lesions.

Aberrant crypt foci in patients with neoplastic and nonneoplastic colonic disease.

Aberrant crypt foci (ACF) are putative preneoplastic lesions that might represent the earliest morphological lesion visible in colonic carcinogenesis. However, findings concerning the growth and morphological features of these lesions in human studies suggest that ACF are highly heterogeneous in nature. In this study, we evaluated the morphological features of a large number of ACF in colon mucosa of 26 patients with colorectal carcinoma (CRC), four patients with adenoma as well as seven patients with nonneoplastic colonic diseases. By dissecting microscope, 508 ACF were identified, and of these, 378 were sampled for histological examination. The median ACF density (number of ACF/cm2) was significantly higher in the left colon than in the right colon (0.047 v 0.014 ACF/cm2). Unexpectedly, in our series, the overall ACF density was higher in the nonneoplastic colonic diseases than in CRC (0.13 v 0.032 ACF/cm2, P=.0087), cases of nonneoplastic diseases, however, being limited to 7 patients. ACF were significantly larger in colons with CRC or adenoma than in colons with nonneoplastic disease (P < .03). On histological examination, we observed 133 ACF with normal epithelium, 189 ACF with hyperplasia, 27 ACF with atypical hyperplasia, and 29 ACF with dysplasia. We noted a progressive increase of median ACF size from normal mucosa to hyperplasia, atypical hyperplasia, and dysplasia. Dysplastic ACF were more frequently observed in patients with CRC or adenoma and showed predominantly elongated crypt orifices (P < .0001). We conclude that ACF are histologically heterogeneous, encompass a spectrum of lesions of which only a subset are associated with dysplasia and then represent an early step in colorectal carcinogenesis. ACF with dysplasia are characterized by larger size, elongated crypt orifices, and an association with CRC.

The natural history of a gastric low grade B cell MALT lymphoma followed during 11 years without treatment.

Low grade B cell mucosa associated lymphoid tissue (MALT) lymphoma of the stomach is usually an indolent tumour that remains localised for a long time before dissemination occurs. MALT appears in the stomach in response to infection by Helicobacter pylori, which is present in 80-90% of cases. The pathogenesis of the evolution from chronic gastritis to malignant lymphoma has not yet been fully explained and the exact role of H pylori in the pathogenesis and progression of gastric lymphoma remains unclear. This report describes the case of a 72 year old woman with a low grade B cell MALT lymphoma localised in the gastric fundus, who refused to be treated for eradication of H pylori. The histological diagnosis of B cell MALT lymphoma was supported by both immunohistochemical and molecular genetic analysis. After 11 years of follow up, this MALT lymphoma remained indolent, without local progression or blastic transformation, and the H pylori infection was still persistent, even though the density of bacteria had decreased drastically. Interestingly, two different clonal immunoglobulin (Ig) gene rearrangements were found in two series of biopsies performed with an interval of 11 years. This case report supports the following notions: (1) H pylori associated gastritis is a risk factor for gastric MALT lymphoma, but might not be sufficient by itself for the progression of the disease, and (2) in the evolution of MALT lymphomas, different cell clones characterised by different Ig rearrangements may emerge.

Microscopic colitis with giant cells: a rare new histopathologic subtype?

Collagenous and lymphocytic colitis might be part of the same disease spectrum. In this report, we present a histopathologic subtype of microscopic colitis characterized by the presence of subepithelial multinucleated giant cells. This reaction is very unusual and not explicable by any underlying disease process or previous treatment. Among 490 cases of microscopic colitis (MC) diagnosed between 1992 and 2002, we found 2 cases with macrophages and giant cells (0.4%). One case of lymphocytic colitis (LC) and 1 case of collagenous colitis (CC) presented aggregates of macrophages and giant cells located in the superficial part of the lamina propria. Infectious or non-infectious colonic granulomatous diseases were excluded on histologic, clinical, and biological grounds. The recognition of this feature in an MC is important to avoid the diagnosis of granulomatous infectious or idiopathic colitis such as Crohn's disease. Even if very unusual, this subtype of MC evolves favorably since the 2 patients responded well to corticosteroid treatment.

[Chemical peritonitis after iatrogenic rupture of a dermoid cyst of the ovary treated by coelioscopy. Apropos of a case and review of the literature]. / Péritonite chimique après rupture iatrogène d'un kyste dermoïde de l'ovaire traité par coelioscopie. A propos d'un cas et revue de la littérature.

Dermoid cyst is the most frequent benign ovarian tumor. Its intraperitoneal rupture may lead to a peritoneal reaction known as chemical peritonitis. It is a rare but a potentially dangerous issue. Its treatment may need one or more reoperations. We report here the case of a patient operated on in emergency for a torsion of an ovarian dermoid cyst, with peritoneal spillage of its content during coeliosurgery. The prolonged contact between the sebaceous material and the peritoneum has led to a chemical peritonitis. Two more laparoscopic interventions, associated with a systemic anti-inflammatory treatment, were necessary to relieve symptoms. We propose the following attitude to avoid this complication: (1) puncture and drainage of the cyst with a trocar; (2) extraction of the cyst in an endobag, and (3) abundant washout of the peritoneal cavity.

Detection of metastatic disease with sentinel lymph node dissection in colorectal carcinoma patients.

BACKGROUND: In curative colorectal cancer surgery, radical lymph node dissection is essential for staging and decision-making for adjuvant treatment. PURPOSE: The aims of the study were to analyse to what extent sentinel lymph node dissection (SLND) in colorectal cancer could upstage N0 patients and how lymphatic mapping could demonstrate micrometastatic disease. PATIENTS AND METHODS: In a prospective study, patients were selected by CT scanning, avoiding bulky disease and distant metastasis. When standard staining (HE) was negative, micrometastases were searched for by immunohistochemistry (cytokeratin 11, CEA and Ca19-9 antibodies). Micrometastatic lymph nodes were classified N+(i). RESULTS: Detection of sentinel lymph nodes was successful in 48 out of 52 colorectal cancer patients. Among the 44 M0 patients, 22 were N0 (i-) and 22 were N+ (13 with standard HE procedure, three were N+ (macrometastasis) with the SN as the only positive node and six patients had 1-4 micrometastatic SN (N+(i)). An overall potential upstaging of 9/44 could be considered after SLND. With a mean follow-up of 48 months survival, analysis showed that disease-specific survival of the group of six N+(i) patients was intermediate between the group of 22 N0 (i-) patients and the group of 16 N+ patients. CONCLUSION: SLND may improve the detection of metastasis in conventionally bivalved nodes. Further studies could assess if micrometastatic disease detected in SN could be integrated into the risk factors for stage II patients in order to consider adjuvant chemotherapy.

Mixed testicular germ cell tumor presenting as metastatic pure choriocarcinoma involving the maxillary gingiva.

Gingival metastases are infrequent and invariably associated with a widespread disease and a poor prognosis. Because of their unremarkable clinical appearance, they can be difficult to distinguish from more common gingival hyperplastic or reactive lesions, such as pyogenic granuloma, peripheral giant cell granuloma, and peripheral ossifying granuloma. We are reporting here an unusual case of a 36-year-old man with a mixed testicular germ cell tumor presenting as a metastatic pure choriocarcinoma involving the maxillary gingiva, extending from the first left premolar to the left second maxillary molar, mimicking a 'benign looking' gingival mass. Gingival metastases may be the first manifestation of a widespread metastatic disease and therefore particular attention must be paid to gingival lesions associated with atypical clinical symptoms and/or signs.

CPT-11 and concomitant hyperfractionated accelerated radiotherapy induce efficient local control in rectal cancer patients: results from a phase II.

Patients with rectal cancer are at high risk of disease recurrence despite neoadjuvant radiochemotherapy with 5-Fluorouracil (5FU), a regimen that is now widely applied. In order to develop a regimen with increased antitumour activity, we previously established the recommended dose of neoadjuvant CPT-11 (three times weekly 90 mg m(-2)) concomitant to hyperfractionated accelerated radiotherapy (HART) followed by surgery within 1 week. Thirty-three patients (20 men) with a locally advanced adenocarcinoma of the rectum were enrolled in this prospective phase II trial (1 cT2, 29 cT3, 3 cT4 and 21 cN+). Median age was 60 years (range 43-75 years). All patients received all three injections of CPT-11 and all but two patients completed radiotherapy as planned. Surgery with total mesorectal excision (TME) was performed within 1 week (range 2-15 days). The preoperative chemoradiotherapy was overall well tolerated, 24% of the patients experienced grade 3 diarrhoea that was easily manageable. At a median follow-up of 2 years no local recurrence occurred, however, nine patients developed distant metastases. The 2-year disease-free survival was 66% (95% confidence interval 0.48-0.83). Neoadjuvant CPT-11 and HART allow for excellent local control; however, distant relapse remains a concern in this patient population.

[Mucinous tumors of the ovary. Anatomo-clinical aspects, histological classification, prognostic factors and histogenesis]. / Les tumeurs mucineuses de l'ovaire. Aspects anatomo-cliniques, classification histologique, facteurs pronostiques et histogenèse.

In contrast with other malignant tumors, the prognosis of malignant ovarian mucinous tumors has not been improved. In fact, their are diagnosed late and their therapy is often inadequate. The absence of consensus concerning the histological criteria of borderline tumors and mucinous carcinomas has led to diverse classifications which are often not reproducible and are also responsible for heterogeneous results concerning patient survival. Unfortunately, none of the biochemical, molecular biology or cytometric markers which have been studied up until now can be used for differential diagnosis. Another particularity of mucinous tumors consists of their association with other ovarian tumors, mural nodules which are reactive or tumor proliferations and which might influence the prognosis of the mucinous tumor, when their are malignant, and peritoneal pseudomyxoma and appendicular mucocele which give rise to problems related to their relation.

Estrogen and progesterone receptors and pS2 and ERD5 antigens in gastric carcinomas from the European population.

We examined immunohistochemically 50 gastric carcinomas from European patients for estrogen receptors, progesterone receptors, and hormone-receptor-related proteins pS2 and ERD5. Unlike gastric carcinomas from non-Europeans reported previously, the carcinomas of the present series were all negative for estrogen and progesterone receptors. One-half of them, however, expressed pS2, and three-fourths were positive for ERD5. pS2 expression was significantly more frequent in carcinomas of the diffuse type than in those of the intestinal type and in advanced carcinomas compared with early ones. Our results indicate that pS2 and ERD5 are estrogen independent in the stomach. The possibility that estrogen and progesterone receptor status could be different in gastric carcinomas from Occidental and non-Occidental patients is discussed.

The role of Helicobacter pylori in primary gastric MALT lymphoma.

AIMS: Helicobacter pylori has been claimed to be an important aetiological factor which raises the risk of mucosa-associated tissue lymphoid (MALT) lymphoma. However, some studies on gastric MALT lymphoma revealed a low rate of H. pylori infection suggesting that not all gastric lymphomas are related to H. pylori infection. The aim of this study was to verify the H. pylori infection frequency in a series of patients with primary gastric MALT lymphomas and to examine the relationship between H. pylori and the pathological features of those lymphomas. METHODS AND RESULTS: Thirty-one cases of resected gastric lymphoma were analysed: 10 cases (32%) were low-grade MALT lymphomas and 21 cases (68%) were high-grade MALT lymphomas. Helicobacter pylori was found in only 18 of 31 (58%) cases. Helicobacter pylori infection was significantly correlated with the grade and depth of invasion of MALT lymphoma since 63% of superficial low-grade MALT lymphomas were positive for H. pylori compared with 38% of advanced high-grade MALT lymphomas (P = 0.02). CONCLUSION: We confirmed the relationship between H. pylori infection and a subset of gastric MALT lymphoma. Our results also showed that not all low- and high-grade gastric MALT lymphomas are H. pylori-dependent. This suggests that H. pylori infection may play a promoter role in the development of MALT lymphoma, but its presence is not mandatory for the progression of the lymphoma in view of its low frequency in advanced high-grade MALT lymphoma.

Expression of telomerase genes correlates with telomerase activity in human colorectal carcinogenesis.

The human telomerase enzyme is composed of two essential components, hTR, which acts as a template for reverse transcription, and hTERT, which is the putative catalytic subunit for the enzyme. Recent studies have demonstrated a good correlation between hTERT expression and telomerase activation, whereas RT-PCR results seemed to reveal that hTR is ubiquitously expressed in all cells. These observations left unclear the role of hTR, and to a lesser extent hTERT, in the regulation of telomerase activation. In the present study, the correlation of telomerase activity and the expression of these genes was examined in a total of 70 colorectal tissues (25 adenocarcinomas, 30 adenomas, and 15 samples of normal colorectal mucosa). Total RNA for RT-PCR analysis and cell extracts for TRAP assay were obtained from consecutive sections and histological control was simultaneously performed. To avoid false-positive results, due to the fact that hTR cDNA and genomic hTR DNA are identical (the gene has no introns), extensive DNase digestion was performed before cDNA synthesis. RT-PCR analysis revealed that hTERT mRNA was expressed in all cancers and in 13 of 14 telomerase-positive adenomas, but never in telomerase-negative colorectal tissues. hTR transcripts were observed in all telomerase-positive samples but also in three telomerase-negative samples, two adenomas, and one normal colonic mucosa. It is concluded that hTERT and hTR expression is strongly correlated with telomerase activity. hTR transcripts, however, also occur in some telomerase-negative tissues and these results are in keeping with the concept that hTERT expression is a major regulator of telomerase activity.

Intratumor genetic heterogeneity in advanced human colorectal adenocarcinoma.

Colorectal carcinogenesis is widely accepted as one of the best-characterized examples of stepwise progression. The existing colorectal carcinogenesis model assumes genetic homogeneity of individual tumors for the main known genetic alterations: K-ras and p53 genes point mutations and loss of heterozygosity (LOH) of chromosome 5q and 18q. The object of the present study was to demonstrate the existence of an intratumor genetic heterogeneity in advanced sporadic colorectal carcinoma for these genetic alterations. Using improved tissue microdissection and DNA extraction, for each tumor, amplifiable DNA was obtained from 15 to 20 areas, of which 1 to 2 concerned lymph node metastases (LNM). This study revealed that 10 of 15 (67%) analyzed tumors were heterogeneous for at least 1 genetic alteration, with between 2 and 6 genotypically different clones detected per tumor. No correlation was observed between the genotype of these subclones and histological differentiation or invasive propensity. Intratumor heterogeneity was more frequently observed for LOH than for point mutations, 67% and 58% for LOH at APC and DCC locus, and 20% for mutation of either the K-ras or p53 gene. In 5 of the 9 (56%) heterogeneous cases with available LNM, the genotype observed in the LNM was different from that of the main clone in the primary tumor, and moreover, 2 of the LNM displayed a genotype undetected in the primary tumor. In conclusion, intratumor genetic heterogeneity was demonstrated in advanced sporadic colorectal carcinoma and was represented as topographically distinct genotypic subclones. Taking into account such a significant genetic heterogeneity of colorectal tumors, the use of genetic markers for prognosis management should be reconsidered.

Gastric mucosal alpha(4)beta(7)-integrin-positive CD4 T lymphocytes and immune protection against helicobacter infection in mice.

BACKGROUND & AIMS: The integrin alpha(4)beta(7) mediates homing of effector/memory lymphocytes to the intestine and the mucosa-associated lymphoid tissue. This study examined the ability of alpha(4)beta(7)(hi) CD4(+) T lymphocytes to home to the stomach and their role in immunization-mediated protection against Helicobacter felis infection. METHODS: Gastric lamina propria and circulating mononucleated cells of naive, infected, and immunized Swiss Webster mice were isolated, and alpha(4)beta(7)-integrin expression was quantified by flow cytometry on CD4(+) T lymphocytes. Anti-alpha(4)beta(7)-integrin antibody was used to block alpha(4)beta(7) function in vivo. RESULTS: In naive mice, alpha(4)beta(7)(hi) CD4(+) T cells were enriched approximately 10-fold in the gastric mucosa compared with peripheral blood (P<0.0001). Chronic H. felis infection did not alter these proportions, but oral immunization with H. felis sonicate plus cholera toxin (CT) or with CT alone markedly increased gastric alpha(4)beta(7)(hi) CD4(+) T cells compared with naive and infected controls (P = 0.0008 and P = 0.002 for H. felis sonicate and CT, respectively). Anti-alpha(4)beta(7)-integrin antibody blocked the protection induced by oral immunization with H. felis sonicate and CT. CONCLUSIONS: The integrin alpha(4)beta(7) participates in the homing of CD4(+) T lymphocytes to the stomach and in the protection of the gastric mucosa against H. felis infection.