CD4+CD25+ T regs with acetylated FoxP3 are associated with immune suppression in human leprosy.

Leprosy is a chronic human disease that results from infection of Mycobacterium leprae. T reg cells have been shown to have important implications in various diseases. However, in leprosy, it is still unclear whether T regs can mediate immune suppression during progression of the disease. In the present study, we have proposed the putative mechanism leading to high proportion of T reg cells and investigated its significance in human leprosy. High levels of TGF-ß followed by adaptation of FoxP3(+) naive and memory (CD4(+)CD45RA(+)/RO(+)) T cells were observed as the principal underlying factors leading to higher generation of T reg cells during disease progression. Furthermore, TGF-ß was found to be associated with increased phosphorylation-mediated-nuclear-import of SMAD3 and NFAT towards BL/LL pole to facilitate FoxP3 expression in these cells, the same as justified after using nuclear inhibitors of SMAD3 (SIS3) and NFAT (cyclosporin A) in CD4(+)CD25(+) cells in the presence of TGF-ß and IL-2. Interestingly, low ubiquitination of FoxP3 in T reg cells of BL/LL patients was revealed to be a major driving force in conferring stability to FoxP3 which in turn is linked to suppressive potential of T regs. The present study has also pinpointed the presence of CD4(+)CD25(+)IL-10(+) sub class of T regs (Tr1) in leprosy.

Adrenal medullary autografts into the basal ganglia of Cebus monkeys: graft viability and fine structure.

Based largely upon studies done in rats, a number of medical centers are now performing autografts of adrenal medullary tissue in consenting patients with Parkinson's disease. However, a systematic experimental evaluation of adrenal medullary autografts in nonhuman primates is necessary. This study provides a detailed analysis of the implant site at the fine structural level 30 days post-transplantation in the Cebus monkey. Five normal and two 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP)-treated Cebus monkeys received adrenal medullary autografts using an open microsurgical approach (n = 3) or via stereotactic placement with a tissue carrier (n = 4). Analysis of preimplant samples of the adrenal medulla confirmed that viable chromaffin cells were implanted into the basal ganglia. However, 30 days later, the implant site resembled a chronic inflammatory focus, with grafted chromaffin cells identified ultrastructurally in only two of the seven transplanted monkeys. The grafted cells showed overt signs of cellular degeneration and were surrounded by phagocytic macrophages. All of the implant sites, regardless of the surgical approach, were filled with macrophages, cells of hematogenous origin, and fibrous astrocytes. The vasculature of the implant site was of the nonfenestrated type, characteristic of the host striatum. Despite the poor survival of implanted chromaffin cells, robust sprouting of tyrosine hydroxylase-like immunoreactive fibers was evident in the striatum adjacent to the implant site (see accompanying manuscript, M.S. Fiandaca, J. H. Kordower, J.T. Hansen, S.-S. Jiao, and D.M. Gash, 1988, Exp. Neurol. 102: 76-91), suggesting that implantation may have precipitated a host response that was beneficial to the transplanted animal. Additional studies that provide a better understanding of the cellular elements residing in the implant site and their potential for trophic influence seem warranted.

Effect of pyridine extraction on the acid fastness of mycobacteria.

The effect of pyridine extraction on mycobacterial acid-fastness has been studied using M. leprae and some cultivable mycobacteria. The results revealed that not only M. leprae but some other mycobacteria, notably, M. vaccae and M. phlei also lose their acid-fastness when extracted with fresh pyridine for 2 hours at room temperature. The implication of these findings is discussed.

Use of pyridine for differentiating Mycobacterium leprae from other mycobacteria in direct microscopy.

The loss of acid-fastness by M. leprae after two-hour pyridine extractions, reportedly a specific test for differentiating M. leprae from all other mycobacteria, was verified on different materials obtained from leprosy patients, histologic sections from a fatal post-BCG vaccination case and smears prepared from pure cultures of 32 strains of 18 different mycobacterial species. Under the conditions used, pyridine extraction led to complete loss of acid-fastness in M. leprae only in histologic sections of biopsy specimens from leprosy patients, whereas in direct smears from skin lesions containing M. leprae the number of acid-fast rods after pyridine extraction was either equal to or only slightly smaller than in control preparations. Moreover, since smears from pure cultures of M. avium, M. diernhoferi, M. fortuitum, M. scrofulaceum, M. vaccae and especially M. phlei displayed a smaller or greater number of nonacid-fast cells as well (in some instances only 10% to 20% of cells were found stained whereas control slides contained 90% to 100% acid-fast rods), loss of acid-fastness after two-hour pyridine extraction cannot be considered a property typical of M. leprae only.