The intestinal immune system and its relation to disease.

The essential protective structure against the heavy enteric antigenic burden, the gut mucosa, prevents penetration of noxious agents, but allows a minimal exchange of large molecules and particles between the gut lumen and the 'milieu intérieur' of the body. M cells in the follicle-associated epithelium of the gut, ideal gateways for the presentation of enteric antigens to the cells of the gut-associated lymphoid tissue (GALT), are also weak links in the mucosal barrier, and may provide access for various microorganisms. The afferent limb of the GALT consists of distinct aggregates of lymphoid cells located in Peyer's patches, the vermiform appendix and the solitary lymphatic follicles, and of the mesenteric lymph nodes. The efferent limb subsumes the diffusely scattered mucosal leukocytes, mainly lymphocytes and plasma cells. Intraepithelial and mucosal T lymphocytes are instrumental in launching local immune responses, producing lymphokines, and in the specific lysis of virally infected cells. Antigenic stimulation of the GALT results in local secretion of antibodies, or in suppression of systemic immunologic responses to ingested antigens ('oral tolerance'). Poorly controlled mucosal immune responses result in organ-specific diseases. Extranodal lymphomas that mimic structures of the GALT may arise on a background of inflammatory or immunologic (autoimmune) disorders.

Induction and progression of human lymphoproliferative lesions by Epstein-Barr virus.

Epstein-Barr virus (EBV) is involved in numerous lymphoproliferative diseases. In addition to classical lesions such as endemic Burkitt's lymphoma and infectious mononucleosis, there are other disorders of the lymphoid system that are discussed in relation to EBV: B-cell lymphomas in immunosuppressed individuals. Hodgkin's disease and, to some extent, primary extranodal lymphomas. Studies of the EBV expression in classical and nonclassical lesions could lead to the better understanding of different EBV mechanisms in lymphomagenesis.

Identification of EBV-DNA in lymph nodes from patients with lymphadenopathy and lymphomas associated with AIDS.

Fourteen examples of non-Hodgkin's lymphoma (NHL) and four of Hodgkin's disease in patients with AIDS as well as lymph nodes exhibiting changes related to the lymphadenopathy syndrome (LAS) from 11 HIV-positive individuals were studied for the presence of Epstein-Barr virus (EBV) genome both by in situ DNA hybridization and blotting techniques. Both methods were performed using formalin-fixed paraffin-embedded material. All the NHLs were of high malignancy and all but one were of the B-cell type. Of the four examples of Hodgkin's disease, two were lymphocytic predominant, one of mixed cellularity and one of the nodular sclerosing variety. The lymph nodes of patients with LAS were mostly stage I with marked follicular hyperplasia. In 7 of the 14 NHLs the presence of EBV-DNA was clearly demonstrated by dot-blotting and by in situ hybridization. All lymph nodes from the patients with LAS and AIDS-related Hodgkin's disease were negative for EBV by dot-blot and in situ hybridization assays. We conclude that EBV plays a role in the development of AIDS-related lymphomas, but the fact that half these lymphomas are EBV-negative suggests that other mechanisms such as polyclonal stimulation of B-cells by HIV products may also be important.