Intravenous apoptotic spleen cell infusion induces a TGF-beta-dependent regulatory T-cell expansion.

Apoptotic leukocytes are endowed with immunomodulatory properties that can be used to enhance hematopoietic engraftment and prevent graft-versus-host disease (GvHD). This apoptotic cell-induced tolerogenic effect is mediated by host macrophages and not recipient dendritic cells or donor phagocytes present in the bone marrow graft as evidenced by selective cell depletion and trafficking experiments. Furthermore, apoptotic cell infusion is associated with TGF-beta-dependent donor CD4+CD25+ T-cell expansion. Such cells have a regulatory phenotype (CD62L(high) and intracellular CTLA-4+), express high levels of forkhead-box transcription factor p3 (Foxp3) mRNA and exert ex vivo suppressive activity through a cell-to-cell contact mechanism. In vivo CD25 depletion after apoptotic cell infusion prevents the apoptotic cell-induced beneficial effects on engraftment and GvHD occurrence. This highlights the role of regulatory T cells in the tolerogenic effect of apoptotic cell infusion. This novel association between apoptosis and regulatory T-cell expansion may also contribute to preventing deleterious autoimmune responses during normal turnover.

Validation of a high sensitive immunoenzymatic assay to establish the origin of immunoglobulins in female genital secretions.

Several studies were carried out to characterize the humoral immune response on mucosal genital surfaces. However, the results obtained so far were particularly conflicting due to the absence of validation methods. The aim of this study was to develop and validate a quantitative ELISA method, which is sensitive and reproducible, to measure immunoglobulin and secretory immunoglobulin concentrations in various biological fluids. This quantitative, sensitive (detection limit = 1 microg/L) and reproducible (coefficient of variation < 15%) method could be of interest to study the effects of viral infections on mucosal non-specific immune response in genital tract. To explore the humoral response, serum, saliva, vaginal secretions, and cervicovaginal secretions from 18 women, 20-45 years old, were evaluated for total-IgA, secretory IgA, IgM, and IgG. Albumin level was also evaluated by immuno-nephelometry. The secretion rates of immunoglobulins were measured by calculating their relative coefficients of excretion by reference to albumin. Despite large individual variations, median immunoglobulin levels were higher in the endocervical secretions than in the cervicovaginal secretions. When we compared the rates of immunoglobulins in genital fluids, IgG prevalence was higher (80%) in cervicovaginal and endocervical secretions than IgA prevalence (12%). In contrast, digestive mucosal secretions, such as saliva, contained mostly IgA (80%). In cervicovaginal and endocervical secretions, IgG and IgM originated mainly from serum, whereas a local synthesis provided total-IgA and secretory IgA. These results allowed us to raise a possible hypothesis for the origin of immunoglobulins in the genital tract. They illustrated the peculiar feature of the female reproductive tract and the difficulty for this tissue to contribute in the mucosal associated lymphoid tissue. The low secretory-IgA and total-IgA levels could explain the particular sensitivity of the vagina and the cervix to infections.

Nonspecific increased serum levels of secretory component in lung tumors: relationship to the gene expression of the transmembrane receptor form.

Polymeric immunoglobulin receptor (pIg-R) is synthesized by epithelial cells lining the bronchial mucosa. It is released in secretions as free secretory component (SC) or bound to Ig as secretory Ig (S-IgA and S-IgM). To evaluate the usefulness of SC and pIg-R expression as tumour markers, we measured SC and secretory Ig, using enzyme-linked immunosorbent assay, in the serum of 45 patients with lung carcinomas, in the serum of 10 patients with non-neoplastic diseases, and in the serum of 45 control subjects. We also studied the immunohistochemical expression of pIg-R and its mRNA in tumors from 20 out of the 45 patients. Serum levels of SC and S-IgA were similarly and significantly elevated in patients with lung cancer (squamous cell carcinoma [25 cases], small cell carcinoma [7 cases], adenocarcinoma [13 cases]) and with non-neoplastic diseases, as compared with control subject levels (P < 0.001). The highest SC levels were found in patients with adenocarcinoma although the mean SC level was not different from other pathologic conditions. pIg-R was usually not detected in the cells of small cell carcinoma or of squamous cell carcinoma, whereas it was found in the cells of five adenocarcinomas and in the two in situ carcinomas under study. The specific mRNA analysis usually agreed with the immunolocalization of pIg-R. A single band at 3.8 kb was detected in the positive tumor tissues and in normal lung tissues. However, the signal was weak in one case of squamous carcinoma and stronger in two out of three adenocarcinomas, than in normal tissues.(ABSTRACT TRUNCATED AT 250 WORDS)