No abstract

SUMMARYThe mechanisms by which immature thymocyte apoptosis is induced during negative selection are poorly defined. Reports demonstrated that cross-linking of T-cell receptor leads to stromal cell activation, expression of inducible nitric oxide synthase (iNOS) and, subsequently, to thymocyte apoptosis. Therefore we examined, whether NO directly or indirectly, through peroxynitrite formation, causes thymocyte apoptosis. Immuno-histochemical detection of nitrotyrosine revealed in vivo peroxynitrite formation in the thymi of naive mice. Nitrotyrosine, the footprint of peroxynitrite, was predominantly found in the corticomedullary junction and the medulla of naive mice. In the thymi of mice deficient in the inducible isoform of nitric oxide synthase, considerably less nitrotyrosine was found. Exposure of thymocytes in vitro to low concentrations (10 m) of peroxynitrite led to apoptosis, whereas higher concentrations (50 m) resulted in intense cell death with the characteristics of necrosis. We also investigated the effect of poly (ADP-ribose) synthetase (PARS ) inhibition on thymocyte apoptosis. Using the PARS inhibitor 3-aminobenzamide (3-AB), or thymocytes from PARS-deficient animals, we established that PARS determines the fate of thymocyte death. Suppression of cellular ATP levels, and the cellular necrosis in response to peroxynitrite were prevented by PARS inhibition. Therefore, in the absence of PARS, cells are diverted towards the pathway of apoptotic cell death. Similar results were obtained with H 2 O 2 treatment, while apoptosis induced by non-oxidative stimuli such as dexamethasone or anti-FAS antibody was unaffected by PARS inhibition. In conclusion, we propose that peroxynitrite-induced apoptosis may play a role in the process of thymocyte negative selection. Furthermore, we propose that the physiological role of PARS cleavage by apopain during apoptosis may serve as an energyconserving step, enabling the cell to complete the process of apoptosis.

General and specific immune function were examined in women with endometriosis. Nonspecific parameters included total leukocyte and differential counts, quantitative immunoglobulin (IgG, IgA, and IgM) determinations, total hemolytic complement, C3, C4, mitogen-induced lymphocyte stimulation, and human leukocyte antigen (HLA) typing; no differences were observed when data were compared to age-matched controls without endometriosis. In contrast, the specific immune response T-lymphocyte-mediated cytotoxicity to autologous endometrial cells was significantly reduced (P less than 0.01) in women with endometriosis. When results from patients were analyzed according to clinical severity of endometriosis, even more striking immunologic alterations were delineated. In addition, lymphocyte stimulation responses to autologous endometrial antigen were lower in patients with severe or moderate disease, approaching statistical significance (P = 0.18 and 0.12, respectively). These studies suggest an immunologic basis for development of endometriosis.

Pediatr. Res. 15: 908-91 1 (1981) Summary MATERIALS AND METHODSIn a review of 13 documented cases of fetal alcohol syndrome (FAS), an increased incidence of Life-threatening bacterial infections as well as a propensity to minor infections was observed. Five of 13 patients had had at least one episode of pneumonia, two had meningitis, and one had sepsis. A comprehensive immunologic evaluation of FAS was completed, and results were compared to an age-matched control group of children with intrauterine growth retardation without FAS.Children SpeculationDefects in host defense and propensity to infection are attributable to intrauterine exposure to high levels of alcohol. Such abnormalities are not related to the degree of postnatal growth retardation nor to degree of malnutrition and do not correct with increasing age. Subsequent disease processes associated with defects in immunity such as malignancy or autoimmunity could result from this exposure to alcohol during fetal development.