Placental Galectins Are Key Players in Regulating the Maternal Adaptive Immune Response

Galectins are potent immunomodulators that regulate maternal immune responses in pregnancy and prevent the rejection of the semi-allogeneic fetus that also occurs in miscarriages. We previously identified a gene cluster on Chromosome 19 that expresses a subfamily of galectins, including galectin-13 (Gal-13) and galectin-14 (Gal-14), which emerged in anthropoid primates. These galectins are expressed only by the placenta and induce the apoptosis of activated T lymphocytes, possibly contributing to a shifted maternal immune balance in pregnancy. The placental expression of Gal-13 and Gal-14 is decreased in preeclampsia, a life-threatening obstetrical syndrome partly attributed to maternal anti-fetal rejection. This study is aimed at revealing the effects of Gal-13 and Gal-14 on T cell functions and comparing the expression of these galectins in placentas from healthy pregnancies and miscarriages. First-trimester placentas were collected from miscarriages and elective termination of pregnancies, tissue microarrays were constructed, and then the expression of Gal-13 and Gal-14 was analyzed by immunohistochemistry and immunoscoring. Recombinant Gal-13 and Gal-14 were expressed and purified, and their effects were investigated on primary peripheral blood T cells. The binding of Gal-13 and Gal-14 to T cells and the effects of these galectins on apoptosis, activation marker (CD25, CD71, CD95, HLA-DR) expression and cytokine (IL-1 beta, IL-6, IL-8, IL-10, IFN gamma) production of T cells were examined by flow cytometry. Gal-13 and Gal-14 are primarily expressed by the syncytiotrophoblast at the maternal-fetal interface in the first trimester, and their placental expression is decreased in miscarriages compared to first-trimester controls. Recombinant Gal-13 and Gal-14 bind to T cells in a population- and activation-dependent manner. Gal-13 and Gal-14 induce apoptosis of Th and Tc cell populations, regardless of their activation status. Out of the investigated activation markers, Gal-14 decreases the cell surface expression of CD71, Gal-13 increases the expression of CD25, and both galectins increase the expression of CD95 on T cells. Non-activated T cells produce larger amounts of IL-8 in the presence of Gal-13 or Gal-14. In conclusion, these results show that Gal-13 and Gal-14 already provide an immunoprivileged environment at the maternal-fetal interface during early pregnancy, and their reduced expression is related to miscarriages

Haematological and immunological changes in cotton mill workers during their shift

SUMMARY. Objectives: To study the haematological and immunological changes in the blood of cotton mill workers during the course of their shift. Method: Blood samples were taken from 70 cotton mill workers before their shift and after 4 hours of cotton dust exposure on the first day of the working week. The following parameters were measured: red blood cells (RBC), haemoglobin (Hb), haematocrit (Ht), mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), red cell distribution width (RDW), platelets (PLT), plateletcrit (PCT), mean platelet volume (MPV), platelet distribution width (PDW), white blood cells (WBC), absolute number and percentage of polymorphonuclear leucocytes, eosinophils and mononuclear leucocytes, IgG, IgA, IgE, IgM, CRP, a2 macroglobulin, haptoglobin, acute-a1glycoprotein, prealbumin, fibronectin, fibrinogen, prothrombin, plasminogen, antithrombin III, a1antitrypsin, C1q, C3c, C4, C5, B-factor, and circulating immune complexes (CIC). Screening was made for the specific IgE against cotton. The level of cotton dust in the workplace was measured by the method of vertical elutriator. Statistical analysis was performed using the paired t-test. Results: Following cotton dust exposure of four hours duration a statistically significant increase was observed in the absolute number and the percentage of polymorphonuclear leucocytes, and in MCHC, PLT, PCT, IgG, IgA, a2 macroglobulin, haptoglopin, fibronectin, fibrinogen, C3c, and C4. There was a statistically significant decrease in the absolute number and the percentage of lymphocytes, eosinophils and monocytes, and in RBC, Hb, Ht, MCV, RDW, C1q and B-factor. No statistically significant changes were observed in IgE, IgM, CRP, acute-a1glycoprotein, prealbumin, prothrombin, plasminogen CIC, antithrombin III, and C5. None of the workers tested positive for the specific IgE against cotton. The level of cotton dust was on average 0.8 mg/m3. Conclusion: After cotton dust exposure an immunological cascade takes place, probably with an acute phase reaction, activation of the classical and alternative complement pathways and possibly with a low degree of haemolysis. It is hypothesized that the main mechanism of the haematological and immunological changes observed in the population under study is a type II hypersensitivity response. Pneumon 2009, 22(4):315-330

Comparative analysis of peripheral natural killer cells in the two phases of the ovarian cycle

Problem: Changes in endometrial Natural Killer (NK) cells during the luteal phase of the ovarian cycle are important in initiating/maintaining a subsequent pregnancy. In the present study it was investigated whether during the menstrual cycle changes occur also in peripheral blood (PB) NKs. Method of study: Blood samples during the follicular and the luteal phase were collected from 30 women without fertility problems. Samples were analyzed by flow-cytometry for: (1) NK cells (CD3-CD16+CD56+) and (2) intracellular production of interferon-γ (IFN-γ) by NK cells. For the comparison and correlation of the two populations between the two phases, Wilcoxon signed-rank test and Spearman's Coefficient were used. Results: The differences in percentages of CD3-CD16+CD56+ cells and that of CD3-CD16+CD56+/IFN-γ+ cells between the follicular and the luteal phase were not statistically significant (10.61 ± 5.11 versus 9.76 ± 4.57 and 6.48 ± 7.90 versus 7.30 ± 6.77, respectively, P > 0.05). The correlation between the two variables (NK% and NK/IFN-γ%) was weakly positive (P = 0.07) only in the follicular phase. Conclusion: The study did not reveal menstrual cycle-depended changes in PB NK cells. Thus, a suggestion to measure these cells in a specific phase of the cycle in order to predict the outcome of a subsequent pregnancy in women with fertility problems is objected. © 2009 John Wiley & Sons A/S

Chlamydia trachomatis infection and V gamma 9V delta 2 T cells in women with recurrent spontaneous abortions

Problem: V gamma 9V delta 2 T cells (.9d2) are involved in antibacterial immune responses. The aim of this study was to look for associations between peripheral blood (PB) gamma 9 delta 2 T cells and cervix/vaginal Chlamydia trachomatis (Ct) infection in women with recurrent spontaneous abortions (RSA). Method of study: Peripheral blood samples were obtained from 201 RSA women within 10 days after they experienced a new miscarriage gamma 9 delta 2 T cells and their percentage in total gamma delta T cells were compared between women who had been found and women who had not been found infected with Ct (last 6 months). Fertile women (82) served as control subjects. Results: The difference of mean percentages of gamma 9 delta 2 T cells between the abortion and control groups, and the Chlamydia (+) and Chlamydia (-) groups was highly statistically significant (P < .00001). Significant difference was also found between the Chlamydia (+) and Chlamydia (-) group and the control group (ANOVA). Conclusion: The measurement of.9d2T cells may be useful to suspect possibly undiagnosed chlamydial infection in RSA women

Recurrent erythema multiforme : tissue typing in a large series of patients

The definitive version can be found at: http://onlinelibrary.wiley.com/ Copyright British Association of Dermatologists & Blackwell [Full text of this article is not available in the UHRA]Previous reports have shown an increased frequency of certain HLA antigens in association with erythema multiforme, including HLA-B15(B62), HLA-B35, HLA-A33, HLA-DR53 and, more recently, HLA-DQB1*0301. A strong association with HLA-DQ3 has been documented in patients with recurrent erythema multiforme. We have performed HLA typing in 39 patients with recurrent erythema multiforme, of whom 33 were associated with herpes simplex virus infection. The results were compared with 309 controls. In the recurrent erythema multiforme patients there was a statistically significant increase in HLA-B62 and HLA-B35. An increase in HLA-DR53 was also found, although this did not reach statistical significance. There was no increase in HLA-A33. The presence of HLA-DQ3 in the study population approached that in the controls. Finally, the study population demonstrated a trend towards a reduction in the HLA antigens A1, B8, and DR3. The study confirms the previously reported associations with HLA-B62 (B15), HLA-B35 and HLA-DR53. We have been unable to confirm an association of HLA-A33 or HLA-DQ3 with erythema multiforme. The HLA antigens A1, B8, and DR3 are associated with autoimmune disease, reflecting an increased host response to tissue self antigens. Their absence in patients with recurrent erythema multiforme (REM) may be an indicator of a poor host response to an antigen, which in the case of REM is the herpes simplex virus.Peer reviewe