Induction of autoimmunity through bystander effects. Lessons from immunological disorders induced by heavy metals.

Autoreactive T cells exist in healthy individuals and represent a potential reservoir of pathogenic effectors which, when stimulated by microbial adjuvants, could trigger an autoimmune disease. Experimental studies have indicated that xenobiotics, well defined from a chemical point of view, could promote the differentiation of autoreactive T cells towards a pathogenic pathway. It is therefore theoretically possible that compounds present in vaccines such as thiomersal or aluminium hydroxyde can trigger autoimmune reactions through bystander effects. Mercury and gold in rodents can induce immunological disorders with autoimmune reactions. In vitro, both activate signal transduction pathways that result in the expression of cytokines, particularly of IL-4 and IFNgamma. In a suitable microenvironment heavy metals could therefore favour the activation of autoreactive T cells. In that respect, genetic background is of major importance. Genome-wide searches in the rat have shown that overlapping chromosomal regions control the immunological disorders induced by gold salt treatment, the development of experimental autoimmune encephalomyelitis and the CD45RC(high)/CD45RC(low)CD4(+)T cells balance. The identification and functional characterization of genes controlling these phenotypes may shed light on key regulatory mechanisms of immune responses. This should help to improve efficacy and safety of vaccines.

[Study of histidine decarboxylase activity (HDC) in murine fetal hematopoietic organs. Description of basophil-enriched splenic cell population during fetal life]. / Etude de l'activité histidine décarboxylase (HDC) dans les organes hématopoïétiques foetaux murins. Description d'une population de cellules spléniques riche en basophiles au cours de la vie foetale.

The role of histamine in vitro during hematopoiesis has been described by several authors. This work was carried out to determine whether histamine could be available in hemopoietic organs by measuring the HDC activity and the histamine content of developing hemopoietic tissues from C 57 BL/6 mice during fetal life (liver from the 12th day of gestation, spleen from the 14th day, and bone-marrow from the 17th day) and postnatal life. High values were found in the liver, the bone marrow, and especially the spleen between the 17th and the 19th days of gestation. A rapid fall in these values was seen near birth. Interestingly, electron microscopy analysis of day 18 fetal spleen cells, provides evidence for a basophil-rich cell population (25%).