Normal epithelial cells modulating HLA class I surface molecules are susceptible to lysis mediated by CD3(+) and CD3(-) "nonspecific" killer cells.

Natural killer (NK) cells and NK-like T cells have been described as efficiently lysing neoplastic cells derived from hematopoietic tumors. By modulating the expression of HLA class I surface molecules on normal epithelial cells, we also observed that nonneoplastic cells can efficiently be lysed by "nonspecific" effectors. Clonal analysis clearly demonstrates that the presence of HLA-specific inhibitory NK receptors, such as CD94, CD158a, and CD158b, described on NK cells, is responsible for the inhibitory signal. Thus, NK cells, as well as NK-like T cells, in the absence of HLA surface molecules on normal target cells, efficiently lyse epithelial cells.

Leuprolide in a 3-monthly versus a monthly depot formulation for the treatment of symptomatic endometriosis: a pilot study.

An open-label randomized pilot study was conducted to evaluate the efficacy and acceptability of 6 months treatment with leuprolide in a 3-monthly versus a monthly i.m. depot injection for the relief of chronic pelvic pain in women with endometriosis. A total of 30 women aged 18-38 years were allocated to the 3-monthly depot arm (n = 15) or to the monthly depot arm (n = 15) after laparoscopic diagnosis of pelvic endometriosis. Mean (SD) deep dyspareunia scores according to a 0-3 point verbal rating scale decreased from 1.8 (0.9) at baseline to 1.3 (0.7) at the end of treatment in the 3-monthly depot group and from 2.1 (1.2) to 1.3 (0.7) in the monthly depot group. Corresponding values in non-menstrual pain scores fell from 2.1 (0.6) to 1.1 (0.3), and from 2.1 (0.8) to 1.2 (0.4) respectively, without statistically significant differences between the groups. Serum luteinizing hormone (LH) and 17 beta-oestradiol concentrations were significantly suppressed at 12 and 24 weeks compared with baseline values, without differences between the groups. The monthly depot caused a slightly more marked inhibition of serum follicle stimulating hormone (FSH) levels with respect to the 3-monthly preparation. Mean (SD) endometriosis scores at baseline and at 6-month follow-up laparoscopy were respectively 32.8 (25.1) and 12.2 (9.3) in the 3-monthly depot group and 29.0 (22.7) and 13.1 (15.3) in the monthly depot group (paired t-test, P < 0.05). Mean percentage decrease in lumbar spine bone mineral density was 5.2% in the former and 4.9% in the latter subjects. In the 3-monthly depot group, 13 women graded the tolerability of their treatment schedule as "good' compared with seven in the monthly depot group (chi 2 = 5.40, P = 0.02).

[Pregnancy in women undergoing a kidney transplant. Our experience and a review of the literature]. / Gravidanza in donne sottoposte a trapianto renale. Nostra esperienza e review della letteratura.

The chances of pregnancy for uremic women are usually very low, because of hormonal balance changes which determine a strong reduction in fertility. Epidemiological studies reveal that pregnancy in hemodialyzed women in fertile patients 4.6-6 months after a well functioning kidney transplant, one fertile transplanted woman over 50 can become pregnant. In the first transplant era, pregnancy after kidney transplant was considered "a big hazard", especially because of the possible side-effects of immunosuppression drugs on foetus development, and the risk of a worsening in the mother's renal function. Therefore, women were strongly recommended to avoid pregnancy. More recently, several reported papers have shown that pregnancy can be safely carried on also by transplanted women, under careful criteria and monitoring. Our experience too, even if limited in number (4 patients) reported in this article confirms this conviction.

Role of major histocompatibility complex class I expression and natural killer-like T cells in the genetic control of endometriosis.

OBJECTIVE: To evaluate whether the expression of human leukocyte antigen (HLA) class I on eutopic and ectopic endometrial cells modify the susceptibility to lysis mediated by lymphocytes. DESIGN: Evaluation of T lymphocyte cytotoxic activity and HLA class I expression on endometrial cells. SETTING: Subjects were recruited at laparoscopy. PATIENTS: Patients with endometriosis (n = 7). Healthy women as controls (n = 10). MAIN OUTCOME MEASURES: Human leukocyte antigen class I molecule analysis of endometrial cells was carried out by immunofluorescence and flow cytometry. Phenotyping of T lymphocytes was performed to analyze T-cell subsets. Cytotoxicity was performed to determine cytolytic activity against endometrial cells. RESULTS: In vitro culture of endometrial cells down-regulates the expression of HLA class I molecules and enhances the susceptibility to lysis mediated by natural killer (NK)-like T lymphocytes. Cytolytic T-cell clones, expressing the CD94 antigen, are inhibited by the HLA-B7 allele on endometrial cells. Ectopic endometrial cells modulate the expression of HLA class I molecules. CONCLUSIONS: The resistance to lysis of endometrial cells is related to expression of surface HLA class I molecules, which send a negative signal for lysis mediated by NK-like T lymphocytes. The HLA-B7 allele inhibits the cytotoxic activity, suggesting that the growth of ectopic endometrial cells might be under a genetic control.

The biological basis of medical treatment of endometriosis.

Efficacy of medical treatment for the management of endometriosis has been documented in several trials, but clinical results cannot always be maintained after the suspension of treatment. Surgical treatment, either laparotomic or laparoscopic, is affected by up to 20% in the recurrence of clinical symptoms after long-term follow-up. The appearance of endometriosis is heterogeneous, its functional status is variable and could lack hormone responsiveness. After medical, surgical or combined treatment the persistence of the failure of defence mechanisms accounts for the recurrence of disease. Unfortunately, all schemes to classify stages of endometriosis have so far failed to identify manifestations of the disease that respond in a predictable way to specific treatments. An analysis of the morphological appearance, implant biological activity and immune system involvement might better define the roles for medical management of endometriosis.

Recombinant interleukin-2 corrects in vitro the immunological defect of endometriosis.

PROBLEM: It has been shown recently that women with endometriosis have several immunological defects. In particular, these patients have a defect in peripheral blood natural killer cell activity and have lost their capacity of recognizing and lysing autologous endometrial cells. METHOD: We evaluated the effect of recombinant interleukin-2 (rIL-2) on peripheral blood lymphocytes obtained from both healthy donors and endometriosis patients. The generation of a strong cytolytic activity against autologous endometrial cells was obtained from both normal donors and endometriosis patients. RESULTS: Interestingly, these cytolytic cells belong to the T-cell lineage and do not recognize both autologous keratinocytes and allogeneic endometrial cells, thus suggesting a mechanism of specific recognition of autologous cells. CONCLUSION: The capability of restoring cytolytic activity using rIL-2 suggests a new immunotherapeutic approach for the treatment of severe endometriosis.