Hsp65-producing Lactococcus lactis prevents experimental autoimmune encephalomyelitis in mice by inducing CD4+LAP+ regulatory T cells.

Heat shock proteins (Hsps) participate in the cellular response to stress and they are hiperexpressed in inflammatory conditions. They are also known to play a major role in immune modulation, controlling, for instance, autoimmune responses. In this study, we showed that oral administration of a recombinant Lactococcus lactis strain that produces and releases LPS-free Hsp65 prevented the development of experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice. This was confirmed by the reduced inflammatory cell infiltrate and absence of injury signs in the spinal cord. The effect was associated with reduced IL-17 and increased IL-10 production in mesenteric lymph node and spleen cell cultures. Hsp65-producing-L. lactis-fed mice had a remarkable increase in the number of natural and inducible CD4+Foxp3+ regulatory T (Treg) cells and CD4+LAP+ (Latency-associated peptide) Tregs - which express the membrane-bound TGF-ß - in spleen, inguinal and mesenteric lymph nodes as well as in spinal cord. Moreover, many Tregs co-expressed Foxp3 and LAP. In vivo depletion of LAP+ cells abrogated the effect of Hsp65-producing L. lactis in EAE prevention and worsened disease in medium-fed mice. Thus, Hsp65-L.lactis seems to boost this critical regulatory circuit involved in controlling EAE development in mice.

Distribution of glial fibrillary acidic protein-immunopositive structures in the developing brain of the turtle Mauremys leprosa.

This study is a continuation of the description of the glial fibrillary acidic protein (GFAP)-immunopositive structures in the adult turtle brain (Kálmán et al. 1994) and presents a comprehensive description of the development of these structures from the 20th embryonic day (E20) to the adult age. GFAP-immunopositive elements were first detected at E28 and by E34 the GFAP-immunopositivity was apparent throughout the brain, except the cerebellum. The appearance of GFAP seemed to be related to the end of cell migration and the formation of the thickened parts of the brain wall, such as the dorsal ventricular ridge. After hatching the pattern of the GFAP-immunopositivity differed from that in the adult only in minute details, except for the brain tracts in which GFAP-pattern was still changing due to myelination, and the molecular layer of the cerebellum in which a transverse fiber system appeared. The GFAP-positive elements belonged originally to the ependymoglia, but later the distortion due to the morphogenetic processes of branching and division changed the pattern almost beyond recognition. In some cases cell bodies--ependymal and non-ependymal--appeared to be GFAP-positive, but no astrocytes (i.e. stellate cells) were detected. The results are discussed in the light of previous observations on developing mammalian, avian and lizard brains.

Time-related decrease of substance P and CGRP in central and peripheral projections of sensory neurones in Mycobacterium leprae infected nude mice: a model for lepromatous leprosy in man.

We have previously shown the depletion of cutaneous calcitonin gene-related peptide (CGRP)- and substance P-containing nerves in human leprosy. The aims of this study were to investigate the temporal effects of leprosy on nerves in skin and spinal cord. Tissues were taken from nude mice, 6 and 12 months after inoculation of Mycobacterium leprae into the hind footpads, and from age-matched controls. Sections were immunostained with antisera to substance P or CGRP. After 6 months of infection, substance P- and CGRP-immunoreactive nerves were reduced in skin from all body areas; by 12 months, the reduction was substantially greater. In the spinal cord, sensory fibres immunoreactive for substance P had decreased compared with controls at 6 and 12 months [by 60 per cent (0.022 mm2) and 80 per cent (0.048 mm2), respectively, P less than 0.001], as with CGRP [30 per cent (0.018 mm2) (P less than 0.02) and 40 per cent (0.028 mm2) (P less than 0.01), respectively]. CGRP immunoreactivity was completely absent in motor neurones after 12 months of infection. Loss of CGRP- and substance P-immunoreactive fibres in skin and spinal cord, and CGRP in motor neurones is in accord with impaired pain sensation and muscle weakness in leprosy.