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N Brousse

Publications and source records attributed to N Brousse.

At least 73 records · Page 4Linked to original sources
PubMed1999

TGF-beta 1 prevents the noncognate maturation of human dendritic Langerhans cells.

TGF-beta 1 is critical for differentiation of epithelial-associated dendritic Langerhans cells (LC). In accordance with the characteristics of in vivo LC, we show that LC obtained from human monocytes in vitro in the presence of TGF-beta 1 1) express almost exclusively intracellular class II Ags, low CD80, and no CD83 and CD86 Ags and 2) down-regulate TNF-RI (p55) and do not produce IL-10 after stimulation, in contrast to dermal dendritic cells and monocyte-derived dendritic cells. Surprisingly, while LC exhibit E-cadherin down-regulation upon exposure to TNF-alpha and IL-1, TGF-beta 1 prevents the final LC maturation in response to TNF-alpha, IL-1, and LPS with respect to Class II CD80, CD86, and CD83 Ag expression, loss of FITC-dextran uptake, production of IL-12, and Ag presentation. In sharp contrast, CD40 ligand cognate signal induces full maturation of LC and is not inhibited by TGF-beta 1. The presence of emigrated immature LCs in human reactive skin-draining lymph nodes provides in vivo evidence that LC migration and final maturation may be differentially regulated. Therefore, due to the effects of TGF-beta 1, inflammatory stimuli may not be sufficient to induce full maturation of LC, thus avoiding potentially harmful immune responses. We conclude that TGF-beta 1 appears to be responsible for both the acquisition of LC phenotype, cytokine production pattern, and prevention of noncognate maturation.

Antigens, CD↗
PubMed1999

Push enteroscopy in celiac sprue and refractory sprue.

BACKGROUND: The aim of this study was to determine in patients with sprue whether jejunal endoscopy improves the diagnostic yield or provides information that may modify management, when compared with evaluation limited to the duodenum. METHODS: From January 1994 to June 1998, a total of 31 patients (6 men, 25 women, mean age 41 years) were prospectively evaluated by push enteroscopy. They were divided into two groups: (1) celiac disease at different stages of activity (n = 23) and (2) refractory sprue (n = 8). The endoscopic and histologic findings in the duodenum and in the jejunum were compared. RESULTS: Celiac disease: In 19 patients, endoscopic and histologic findings in the duodenum and jejunum were similar; in four patients villous atrophy was more severe in the duodenum than in the jejunum. Refractory sprue: In 5 of 8 patients, enteroscopy revealed ulcerative jejunitis, whereas ulcerations were found in the duodenum in only one case. CONCLUSION: In refractory sprue, push enteroscopy with jejunal biopsies was of diagnostic value in 50% of cases demonstrating ulcerative jejunitis, whereas it did not modify the management of patients with responsive celiac disease.

Adult↗
PubMed1999

Up-to-date evolution of small bowel transplantation in children with intestinal failure.

PURPOSE: The aim of the authors was to report an up-to-date review of their experience with 26 intestinal transplantations in children since 1987. METHODS: A retrospective study was conducted of 26 patients with a mean age of 5 years (range, 0.3 to 14 years). Three groups were isolated. In group A (1987 to 1990), seven patients received nine isolated intestinal transplants for short bowel syndrome. Immunosuppression therapy consisted of cyclosporine, aziathioprine, and corticosteroids. In group B (1994-current), nine patients received nine isolated intestinal transplants for short bowel syndrom (n = 2), intestinal pseudoobstruction (n = 2), neonatal intractable diarrhea (n = 3), and Hirschsprung' disease (n = 1); hepatic biopsy results showed weak cholestasis or fibrosis. In group C (1994-current), 10 patients received 10 combined liver-small bowel transplants for short bowel syndrome (n = 3), neonatal intractable diarrhea (n = 4), and Hirschsprung' disease (n = 3); hepatic cirrhosis related to total parenteral nutrition (TPN) was shown in all cases. Groups B and C received immunosupressive treatment consisting of tacrolimus, aziathioprine, and corticosteroids. Posttransplant follow-up included intestinal biopsies of the small bowel twice a week and more frequently or combined with liver biopsy if rejection was suspected. RESULTS: Overall patient survival (PS) and graft survival (GS) are 61% (16 of 26) and 50% (13 of 26), respectively. In group A, severe intestinal allograft rejection occurred in six patients leading to graft removal (GS, 11%). Five patients died of TPN complications after graft removal (PS, 28%). One survivor is off TPN, and one currently is waiting for a second graft. In group B, six patients survived (PS, 66%). Causes of death include hepatic failure (n = 1), renal and liver failure (n = 1), and systemic infection (n = 1). Severe intestinal allograft rejection occurred in five patients, which neccessitated aggressive immunosuppression (antilymphocyte serum) leading to an incomplete functional recovery of the graft. Only two patients currently are off TPN. In group C, eight patients survived (PS, 80%) all of which are currently off TPN. One patient died during the procedure, and one died of severe systemic infection. Intestinal graft rejection occurred in six patients; rejection of the liver allograft occurred in five patients, yet all rejections were weak and successfully treated by corticosteroids (GS, 80%). CONCLUSIONS: Intestinal transplantation is a valid therapeutic option for children with definitive intestinal failure and not only for short bowel syndrome. Tacrolimus improves graft and patient survival (group A v group B). The lower severity of graft rejection in combined liver-small bowel transplantation improves functional results of intestinal transplantation in children without additional mortality or morbidity (group B vgroup C).

Adolescent↗
PubMed1999

Fludarabine alone compared to CHVP plus interferon in elderly patients with follicular lymphoma and adverse prognostic parameters: a GELA study. Groupe d'Etudes des Lymphomes de l'Adulte.

BACKGROUND: Fludarabine was associated with a good response and was well tolerated in patients with follicular lymphoma in phase II trials and this treatment may be associated with less adverse events than treatment with CHVP plus interferon in elderly patients. PATIENTS AND METHODS: One hundred thirty-one patients older than 59 years with a follicular lymphoma and poor prognosis were randomized between the association of CHVP (12 cycles in 18 months) plus interferon (5 MU TIW for 18 months) or fludarabine alone (25 mg/m2/d x 5 days for 6 cycles, then 20 mg/m2/day for 6 further cycles for 18 months). Poor prognosis was defined by the presence of a large tumor mass, poor performance status, the presence of B symptoms, above normal LDH level, or > or = 3 mg/l beta-microglobulin level. RESULTS: Patients treated with CHVP plus interferon had a higher response to treatment, a longer time to progression and a longer survival than those treated with fludarabine alone (P < 0.05 for all analyses). With a median follow-up of 29 months, the 2-year failure-free survival was 63% for the CHVP-plus-interferon arm compared to 49% for the fludarabine arm and the two-year survival was 77% and 62%, respectively. This benefit was confirmed in a multivariate analysis including initial prognostic parameters. Fludarabine alone was associated with less neutropenia than CHVP plus interferon. Interferon was decreased or stopped in 39% of the patients because of severe fatigue. CONCLUSIONS: CHVP plus interferon over 18 months was associated with a better outcome, even though the combination of interferon plus chemotherapy was less well tolerated than fludarabine.

Aged↗
PubMed1999

Chronic intestinal pseudo-obstruction syndrome in pediatric patients.

The aim of this study was to report the presentation and outcome of 22 consecutive children (13 female) who presented with a syndrome of chronic intestinal pseudo-obstruction with or without urinary tract involvement. We analyse the main clinical and histopathological features and discuss therapeutic management. Ten patients had signs of intestinal obstruction at birth, in which 6 presented antenatally with megacystis on ultrasound. Six children presented with constipation and/or obstruction between 1 and 6 months of age and in 6 other patients diagnosis was made between the ages of 1 and 12 years. There was a family history in 4 patients. Investigations showed diffusely dilated gut on x-ray with slow transit on small bowel follow through. Absent or abnormal motor migrating complex with low amplitude contractions were demonstrated on duodeno-jejunal manometry in 12/13. Megacystis occurred in 15/21 and megaureter in 2/21. Full thickness biopsies (n = 22) revealed involvement of muscle layers in 8, and abnormal myenteric plexus on histochemistry in 13. In 1, the biopsies were inconclusive. Recurrent urinary tract infections occurred in all with structural urinary tract abnormality and most had bacterial overgrowth. Severe recurrent episodes of obstruction which required parenteral nutrition (PN) occurred in all patients. Drugs were unhelpful and decompression ileostomies or colostomies were performed in 20/22. Five children died from sepsis (n = 3) or sudden death. Eleven patients remain partially or totally dependent on PN despite decompression ileostomy in 10/11. Six patients underwent colectomy and ileorectal pull-through, 2 of which remain on long-term PN, while the others are totally orally fed. Despite careful histological study pointing to 2 main forms, myopathy and neuropathy, the etiology of primary intestinal pseudoobstruction syndromes remains unknown. It may present antenatally while most of the time the gut and the urinary tract are diffusely involved. The condition has a high morbidity with a percentage requiring long-term PN. Although the mortality rate is high (23%), careful treatment of urinary tract infections and bacterial overgrowth, decompression surgery and judicious use of PN allows survival to adult life.

Child↗
PubMed1999

ICAM-3 and E-selectin endothelial cell expression differentiate two phases of angiogenesis in infantile hemangiomas.

Cellular adhesion molecules are newly identified mediators of angiogenesis. Infantile hemangiomas, characterized in the early stages by a proliferation of poorly differentiated vessels followed in the late stages by a vascular differentiation and regression of the tumor, represent an interesting model to study angiogenesis. We studied by immunohistochemistry the distribution of HLA-DR and three adhesion molecules ICAM-3, E-selectin and VCAM-1 on endothelial cells in different stages of vessel differentiation in infantile hemangiomas. We found high levels of ICAM-3 expression on proliferating vessels, while its expression was low or undetectable on well differentiated vessels. A different set of E-selectin antibodies showed a more heterogenous pattern of distribution and VCAM-1 antigens were found in both proliferating and differentiated vessels. HLA-DR expression on endothelial cells was inversely correlated to the vascular differentiation. Our results are consistent with the hypothesis that ICAM-3 plays a role in the early stages of vessel formation. Our results also suggest that variation of E-selectin and HLA-DR expression may be related either to vessel differentiation or may reflect the acquisition of an activated endothelial cell status.

Antigens, CD↗
PubMed1999

Two unusual tumors in a patient with xeroderma pigmentosum: atypical fibroxanthoma and basosquamous carcinoma.

Xeroderma pigmentosum (XP) is a rare autosomal recessive disease, characterized by a genetic defect in DNA repair. The consequence is a high incidence of skin cancers on sun-exposed cutaneous surfaces of affected children. First lesions appear in the first years of life: telangiectasia, actinic keratosis and keratoacanthomas. Squamous cell and basal cell carcinomas are the most frequent neoplasms. We report the case of a 6-year-old girl affected with XP, who developed two unusual tumors: an atypical fibroxanthoma and a basosquamous carcinoma. In both tumors, immunohistochemical study showed abnormal accumulation of the p53 protein, suggesting the presence of mutation of the p53 tumor suppressor gene. Such p53 mutations may be ultraviolet (UV)-induced, as they are frequently observed in tumors occurring in XP.

Biomarkers, Tumor↗
PubMed1999

Low-grade stage III-IV follicular lymphoma: multivariate analysis of prognostic factors in 484 patients--a study of the groupe d'Etude des lymphomes de l'Adulte.

PURPOSE: To identify the prognostic factors that influence overall survival (OS) in patients with stage III-IV follicular lymphomas and evaluate the clinical usefulness and the prognostic value of the International Prognostic Index (IPI). PATIENTS AND METHODS: Four hundred eighty-four patients with Ann Arbor stage III-IV follicular lymphomas treated in two phase III trials from 1986 to 1995 were screened for this study. All histologic slides were reviewed by two hematopathologists. The influence of the initial parameters on survival was defined by univariate (log-rank test) and multivariate (Cox model) analyses. RESULTS: The poor prognostic factors for OS (age > 60 years, "B" symptom(s), > or = two extranodal sites, stage IV disease, tumor bulk > 7 cm, at least three nodal sites > 3 cm, liver involvement, serous effusion-compression or orbital/epidural involvement, and erythrocyte sedimentation rate > 30 mm/h) that were significant in univariate analysis were subjected to multivariate analysis. Three factors remained significant: B symptom(s) (risk ratio = 1.80), age greater than 60 years (risk ratio = 1.60), and at least three nodal sites greater than 3 cm (risk ratio = 1.71). When the IPI was applied to these patients, the score was 1, 2, 3, and 4-5 in 49%, 39%, 11%, and 2%, respectively, and it was significant for progression-free survival (P =.002) and OS (P =.0001). CONCLUSION: Three prognostic factors for poor OS were identified: B symptoms, age greater than 60 years, and at least three nodal sites greater than 3 cm. The IPI was prognostic for OS, but in this population, a very low number of patients belonged to the high-risk groups.

Adult↗
PubMed1999

Immunohistologic and morphometric analysis of cytotoxic T lymphocytes in gingivitis.

BACKGROUND: Gingivitis is an inflammatory phenomenon localized in gingival tissues and histologically characterized by an infiltration of several inflammatory cell populations. The purpose of this study was to characterize, localize, and quantify in situ inflammatory and cytotoxic T lymphocytes using immunolabeled gingival tissue sections in order to specify their implication during human gingivitis, since it is well known that such cells play an important role in the defense against bacterial elements. METHODS: Paraffin gingival tissue sections from 7 patients with gingivitis (G) and from 7 clinically and histologically healthy controls (C) were immunohistochemically stained by specific antibodies (anti-CD45, anti-CD3, anti-CD8, anti-CD20, anti-TIA-1, anti-GrB, and anti-CD68), allowing the quantification of inflammatory cells in upper gingival epithelium (Ep), in the basal epithelium layer (BEp), and in upper connective tissue (CT). Collagen fibers were stained by sirius red F3Ba in order to evaluate, by morphometric and automated image analysis, the surface occupied by collagen bundles and to histologically confirm the absence of pathology of the clinically selected healthy controls. RESULTS: In the gingivitis group, CD45+, CD3+, CD8+, TIA-1+, and GrB+ lymphocyte numbers were significantly increased in Ep (P<0.05); and CD45+, CD3+, and TIA-I+ lymphocyte numbers were significantly increased in BEp (P <0.05) compared respectively to Ep and BEp of group C. In Ep of group G, mean CD8+/CD3+ cell ratio was significantly increased (P<0.05) compared to BEp and CT, and 25% of TIA-1+ cytotoxic cells were activated GrB+ cells. CONCLUSIONS: The present study suggests that intraepithelial cytotoxic T lymphocytes play an important role during gingivitis and CD8 expression and that activation of TIA-1+ cytotoxic cells could be induced in Ep in response to epithelial environment. Thus, gingival epithelial tissue, which is generally only considered as a physical barrier, in fact contains numerous immune cell populations preventing the infiltration of pathogenic elements into the connective tissue. Particular clinical attention must be taken for the preservation of the epithelial tissue integrity.

Adolescent↗
PubMed1999

[Can intestinal transplantation constitute treatment for intestinal failure?].

The management of patients with intestinal failure has benefited from progress in parenteral nutrition (PN), especially home-based parental nutrition. Intestinal transplantation is now possible and in some conditions, constitutes the logical treatment option. Since 1985, more than 300 small-bowel grafts have been performed, involving the isolated small bowel with or without the colon (45%), the liver + small bowel (40%) or several organs (15%). 2/3 of recipients were under 20 years of age, and indications were short-bowel syndrome (64%), severe intractable diarrhea (13%), abdominal cancer (13%), or chronic intestinal pseudo-obstruction syndrome (8%). 51% of patients survived > 2 years after the graft. Patient and graft survival depends on the type of immunosuppression, i.e. Cyclosporine or FK 506. The results must be interpreted carefully as they represent the first experience in numerous centers using different immuno-suppressive protocols, without any randomization. The results from the largest of these centers more closely reflect the current situation and may exceed a 70% 2-year survival rate. Functional grafts lead to gastrointestinal autonomy (weaning of PN) while maintaining satisfactory nutritional status and normal growth in childhood. Intestinal transplantation is theoretically indicated for all patients permanently or persistently dependent on PN. However, as PN is generally well tolerated, even for long periods, each indication for transplantation must be carefully weighed up in terms of the iatrogenic risk and quality of life. When PN has reached its limits, especially those associated with vascular, infectious, hepatic or metabolic complications, intestinal transplantation must be undertaken. Transplantation of the small bowel alone remains the first option, as combined liver-small bowel grafting is only indicated in case of life-threatening progressive cirrhogenic liver disease.

Adolescent↗
PubMed1998

Highly restricted human T cell repertoire in peripheral blood and tissue-infiltrating lymphocytes in Omenn's syndrome.

Omenn's syndrome is an inherited human combined immunodeficiency condition characterized by the presence of a large population of activated and tissue-infiltrating T cells. Analysis of the TCRB repertoire revealed a highly restricted TCRBV usage in three patients. More strikingly, T cell clones from the three patients expressed TCRB chains with VDJ junction similarities, suggesting a common antigenic specificity. Analysis of the TCRA repertoire in one patient also revealed a restricted TCRAV usage. Finally, analysis of the TCRBV repertoire of tissue-infiltrating T cells in one patient suggested nonrandom tissue migration. These results suggest that the oligoclonal expansion of T cells observed in Omenn's syndrome could be the consequence of autoimmune proliferation generated by a profound defect in lymphocyte development.

Humans↗
PubMed1998

Transforming growth factor beta1, in the presence of granulocyte/macrophage colony-stimulating factor and interleukin 4, induces differentiation of human peripheral blood monocytes into dendritic Langerhans cells.

Langerhans cells (LCs) are dendritic cells (DCs) that are present in the epidermis, bronchi, and mucosae. Although LCs originate in bone marrow, little is known about their lineage of origin. In this study, we demonstrate that in vitro LCs may originate from monocytes. Adult peripheral blood CD14+ monocytes differentiate into LCs (CD1a+, E-cadherin+, cutaneous lymphocyte-associated antigen+, Birbeck granules+, Lag+) in the presence of granulocyte/macrophage colony-stimulating factor, interleukin 4, and transforming growth factor beta1 (TGF-beta1). This process occurs with virtually no cell proliferation and is not impaired by 30 Gy irradiation. Selection of monocyte subpopulations is ruled out since monocyte-derived DCs can further differentiate into LCs. Our data suggest that in vivo LC differentiation may be induced peripherally, from a nonproliferating myeloid precursor, i.e., the monocyte, in response to a TGF-beta1-rich microenvironment, as found in the skin and epithelia. Therefore, the monocyte may represent a circulating precursor critical to the immune response in vivo.

Cell Differentiation↗
PubMed1998

Changes in function of antigen-specific lymphocytes correlating with progression towards diabetes in a transgenic model.

Mice that express influenza hemagglutinin under control of the rat insulin promoter (INS-HA) as well as a class II major histocompatibility complex (MHC)-restricted HA-specific transgenic TCR (TCR-HA), develop early insulitis with huge infiltrates, but progress late and irregularly to diabetes. Initially, in these mice, INS-HA modulates the reactivity of antigen-specific lymphocytes, such that outside the pancreas they do not cause lethal shock like their naive counterparts in single transgenic TCR-HA mice, when stimulated with high doses of antigen. Inside the pancreas, the antigen-specific cells do not initially attack the islet cells, and produce some IFN-gamma as well as IL-10 and IL-4. Spontaneous progression to diabetes, which can be accelerated by cyclophosphamide injection, is accompanied by a 10-fold increase in IFN-gamma and a 3-fold decrease in IL-10 and IL-4 production by the locally residing antigen-specific T cells. Also, total islets from non-diabetic mice contain more TNF-alpha, compared with diabetic mice. This scenario is consistent with the view that beta cell destruction depends upon the increased production of certain pro-inflammatory cytokines by infiltrating T cells. Our inability to detect Fas expression on beta cells, but not on lymphoid cells, in diabetic and non-diabetic mice, puts some constraints on the role of Fas in beta cell destruction.

Animals↗
PubMed1998

Treatment of recalcitrant plaque psoriasis with a humanized non-depleting antibody to CD4.

The presence of activated CD4(+) T lymphocytes in psoriatic skin plaques suggests an immune-mediated pathogenesis for the disease. Six patients with recalcitrant plaque psoriasis (PASI>12) received a humanized non-depleting monoclonal antibody to CD4 (ORTHOCLONE OKT(R)cdr4a). The antibody was well tolerated. Four weeks from treatment, the mean decrease in PASI score was 46%. In three patients disease remission was prolonged for up to 6 months and, in one case, up to 1 year post-treatment. In all patients, circulating CD4+ T-cell counts remained normal and peripheral OKTcdr4a-coated CD4+ lymphocytes were detected up to 10 days after antibody infusion. These results point to the relevance of CD4+ lymphocytes in psoriasis. They also emphasize that depletion of CD4+ cells is not mandatory to achieve therapeutic effectiveness.

Adult↗
PubMed1998

[Prevention of intestinal allograft rejection by anti-adhesion molecule antibodies in a mouse model].

STUDY AIM: Small bowel transplantation is still hampered by a high morbidity and mortality linked to the heavy non specific immunosuppression which is required by the transplantation of this lymphoid organ. Adhesion molecules appear to be potential targets for specific immunosuppression. The aim of the study was to investigate the effect of a transitory administration of anti-LFA-1 or anti-alpha 4 monoclonal antibodies (mAb) in the prevention of rejection in a model of fetal small-bowel transplantation in mice. MATERIALS AND METHODS: The small bowel of C57BL/6 (H-2b) fetus (16 to 20 days of gestation) was transplanted into adult C3H/He mice (H-2k) or C57BL/6 recipient mice. Recipients were treated with a short course of either anti-LFA-1 mAb alone, either with anti-alpha 4 mAb alone, or with both mAb. Biopsies with histological study of the grafts were performed between post-operative day 5 and 60. A score of development and rejection was assigned to each sample. RESULTS: Normal intestinal development with no sign of rejection was observed in 24/28 syngenic grafts till post-operative day 45. In the absence of treatment, intense rejection was observed as soon as day 5 and all allogenic grafts were rejected (n = 22). In contrast, in anti-LFA-1 mAb treated mice, 18/20 allogenic grafts developed normally with minimal signs of rejection. In anti-alpha 4 treated mice, a transient protective effect on small bowel allograft survival was observed on day 7 but thereafter, all grafts were massively rejected within a few days (n = 18). The combination of both mAb didn't improve the survival of the grafts when compared to anti-LFA-1 mAb treated grafts (n = 10). CONCLUSION: These results demonstrate that a transitory administration of anti-LFA-1 mAb, but not of anti-alpha 4 mAb, is able to prolong significantly the survival of non vascularized small bowel fetal grafts in mice. Our results are promising for the possible use of the anti-LFA-1 mAb in clinical intestinal transplantation.

Animals↗
PubMed1998

Homing receptor alpha4beta7 integrin expression predicts digestive tract involvement in mantle cell lymphoma.

Appropriate staging and evaluation of residual disease is critical to improving the treatment of patients with lymphoma. The specific expression of homing receptors may determine the preferential dissemination pattern of tumoral cells. We investigated the expression of the mucosal homing receptor alpha4beta7 on tumoral cells from peripheral lymph node in patients with newly diagnosed mantle cell lymphoma (MCL) to check whether it is associated with gastrointestinal involvement. Expression of the alpha4beta1 integrin and the peripheral lymph node addressin CD62L were also examined. Thirteen MCL patients presenting with peripheral lymphadenopathy were studied. Expression of the mucosal homing receptor integrin alpha4beta7 by peripheral lymph node lymphoma cells was found to be frequent (5/13) and associated with gastrointestinal involvement (5/7). In contrast, lymphoma cells from patients without gastrointestinal involvement did not express alpha4beta7 (6/6) (P = 0.03). These data suggest that alpha4beta7 integrin is expressed by a subset of MCLs and that its expression may predict digestive tract involvement in MCL, furnishing a basis for recognizing two distinct clinical and phenotypic forms, ie, "digestive homing (or digestive primitive)" versus "peripheral" MCL. Further studies on more patients will be needed to understand the impact of biological differences on the prognosis of these two clinical forms.

Aged↗
PubMed1998

Abnormal intestinal intraepithelial lymphocytes in refractory sprue.

BACKGROUND & AIMS: The etiology of refractory sprue is unclear. To gain insight into its pathogenesis, the phenotype and T-cell receptor (TCR) gene rearrangement status of intestinal lymphocytes were analyzed in a group of patients with clinical or biological features of celiac disease but either initially or subsequently refractory to a gluten-free diet. METHODS: Intestinal biopsy specimens were obtained from 26 adults: 6 patients with refractory sprue, 7 patients with active celiac disease, and 13 normal controls. The phenotype of intestinal lymphocytes was studied by immunohistochemistry and, in 3 patients with refractory sprue, by cytometry of lymphocytes purified from intestinal biopsy specimens. TCR rearrangements were assessed by studying TCRgammaV-J junctional regions from DNA extracted from intestinal biopsy specimens and purified intestinal lymphocytes. RESULTS: In the 6 patients with refractory sprue, but not in normal controls or patients with active celiac disease, the intestinal epithelium was massively infiltrated by small lymphocytes that lacked CD8, CD4, and TCR, contained intracytoplasmic but not surface CD3epsilon chains, and exhibited restricted TCRgamma gene rearrangements. CONCLUSIONS: Refractory sprue is associated with an abnormal subset of intraepithelial lymphocytes containing CD3epsilon and restricted rearrangements of the TCRgamma chain but lacking surface expression of T-cell receptors.

Adult↗