Gamma interferon production by bovine gamma delta T cells following stimulation with mycobacterial mycolylarabinogalactan peptidoglycan.

A large percentage of lymphocytes in the blood of cattle express the gamma delta T-cell receptor, but specific functions for these cells have not yet been clearly defined. There is evidence, however, that human, murine, and bovine gamma delta T cells have a role in the immune response to mycobacteria. This study investigated the ability of bovine gamma delta T cells to expand and produce gamma interferon (IFN-gamma) in response to stimulation with mycobacterial products. Bovine gamma delta T cells, isolated from the peripheral blood of healthy cattle, expanded following in vitro stimulation with live mycobacteria, mycobacterial crude cell wall extract, and Mycobacterium bovis culture filtrate proteins. In addition, purified gamma delta T cells, cocultured with purified monocytes and interleukin-2, consistently produced significant amounts of IFN-gamma in response to mycobacterial cell wall. The IFN-gamma-inducing component of the cell wall was further identified as a proteolytically resistant, non-sodium dodecyl sulfate-soluble component of the mycolylarabinogalactan peptidoglycan.

Toll-like receptor 4 plays no role in susceptibility of mice to Mycobacterium tuberculosis infection.

Although various members of the pattern recognition Toll-like receptor (TLR) family have been implicated in host resistance to Mycobacterium tuberculosis infection, it remains unclear if the TLR4 receptor plays an important role. We demonstrate here that infection of TRL4-competent and TLR4-deficient mice on the C3H inbred mouse strain background had similar outcomes, measured in terms of the course of the disease, cell accumulation patterns in the lungs, and lung histopathology. These data argue against a significant role for TLR4 in immunity to tuberculosis in the mouse model.

Activation marker expression on bovine peripheral blood gammadelta T cells during post-natal development and following vaccination with a commercial polyvalent viral vaccine.

Understanding the immunological function of bovine gammadelta T cells is essential for evaluating their role in the response to infectious agents and for determining the potential of targeting this population with vaccines. This study examined the age dependent changes of circulating CD2(+) and CD2(-) gammadelta T cells as well as differences in the expression of activation markers between these two populations. Changes in activation marker expression following vaccination with Vira Shield 5 are also discussed. CD62L was expressed on all CD2(-) gammadelta T cells but only a subset of CD2(+) gammadelta T cells and following vaccination there was a significant decrease in the percentage of CD2(-)/CD62L(+) gammadelta T cells but not CD2(+)/CD62L(+) gammadelta T cells. Both CD2(-) and CD2(+) gammadelta T cells consistently expressed high levels of CD44. The majority of both CD2(-) and CD2(+) gammadelta T cells also expressed CD45R, however, more of the CD2(-) cells were CD45R(neg/lo). Following vaccination there was a significant decrease in the percentage of CD2(-) and CD2(+) gammadelta T cells that expressed CD44 and CD45R. These data indicate significant differences in activation expression on CD2(-) and CD2(+) gammadelta T cells, which adds to the growing evidence that there may be functional as well as phenotypic differences between these two populations of bovine gammadelta T cells.

Cutaneous metastases of a mammary carcinoma in a llama.

An 8-year-old, female llama was evaluated for nonhealing, ulcerative, cutaneous lesions, which also involved the mammary gland. Biopsies of the lesions distant from and within the mammary gland area revealed an aggressive carcinoma. The tumor was confirmed at necropsy to be a mammary gland adenocarcinoma with cutaneous metastasis.

Temporal and spatial arrangement of lymphocytes within lung granulomas induced by aerosol infection with Mycobacterium tuberculosis.

The progression of the immune response in the lungs after aerosol infection with Mycobacterium tuberculosis is a complex cellular event dominated by macrophages and lymphocytes. Although the phenotype of lymphocytes participating in this response is becoming increasingly well characterized, the dynamic influx of these cells during the infection and their spatial arrangements within the lung tissue are still poorly understood. This study shows that in the first month after aerosol infection with M. tuberculosis there was a steady increase in the percentages of total CD3+, CD3+ CD4+ and CD3+ CD8+ cells, with consistently larger numbers of CD3+ CD4+ cells than of CD3+ CD8+ cells. As granuloma formation continued, the granuloma was found to consist of macrophages, CD4, and CD8 T cells, as well as a smaller number of B cells. Whereas CD4 T cells formed organized aggregates, CD8 T cells were fewer and more scattered and tended to be more prominent toward the periphery of the granulomas. The possible ramifications of the juxtapositions of these two major T-cell subsets are discussed.

Lack of protection in mice and necrotizing bronchointerstitial pneumonia with bronchiolitis in guinea pigs immunized with vaccines directed against the hsp60 molecule of Mycobacterium tuberculosis.

In this study, the hsp60 and hsp70 heat shock protein antigens of Mycobacterium tuberculosis were tested as potential vaccine candidates, using purified recombinant protein antigens or antigens encoded in the form of a DNA plasmid vaccine. Guinea pigs vaccinated with a mixture of the two proteins showed no evidence of resistance to low-dose aerosol challenge infection and quickly developed severe lung damage characterized by necrotizing bronchointerstitial pneumonia and bronchiolitis. As a result, we turned instead to a DNA vaccination approach using a plasmid encoding the hsp60 antigen of M. tuberculosis. Although immunogenic in mice, vaccination with plasmid DNA encoding hsp60 was not protective in that model or in the guinea pig model and again gave rise to similar severe lung damage. This study seriously questions the safety of vaccines against tuberculosis that target highly conserved heat shock proteins.

Relative contributions of distinct MHC class I-dependent cell populations in protection to tuberculosis infection in mice.

A necessary role for cytotoxic T lymphocytes in protection against Mycobacterium tuberculosis (MTB) has been suggested by studies of the beta2-microglobulin-deficient mouse, which is unable to present antigens through MHC class I and class I-like molecules and invariably succumbs early after infection. To identify the relative contributions of distinct putative MHC class I-dependent cell populations in protection against tuberculosis, we compared a variety of gene-disrupted mouse strains for susceptibility to MTB infection. Among the strains tested, the most susceptible mice, as measured by survival time and bacterial loads, were the beta2-microglobulin(-/-), followed by transporter associated with antigen processing deficient (TAP1(-/-)), CD8alpha(-/-), perforin(-/-), and CD1d(-/-) mice. These findings indicated that (i) CD8(+) T cells contribute to protection against MTB, and their protective activity is only partially dependent on perforin; (ii) beta2-microglobulin-dependent T cell populations distinct from CD8(+) T cells also contribute to anti-MTB immunity; and (iii) protective immune mechanisms are predominantly TAP-dependent, although TAP-independent mechanisms also contribute to protection. Because CD1d-deficient animals were fully resistant to MTB, other TAP-independent mechanisms must contribute to protection. We suggest here that both classical and nonclassical MHC class I-restricted T cells, distinct from CD1d-restricted cells, may be involved in protective immune responses against tuberculosis.

Treatment of infection with the use of carbon dioxide laser: a 10-year experience.

Despite technical advances in the surgical treatment of infected wounds, this surgery remains a serious problem as it represents more than 27% of infection complications. In the majority of these operations, the wounds are left open and patients undergo long treatments of antibiotics. When the carbon dioxide laser technique was introduced in our country in 1984, it was tested using quantitative bacteriology: it was shown that when used on infected wounds, it reduced the bacterial population of these lesions to low levels with low tissue injury. At our center, between August 1984 and 1994, 539 patients with infected wounds were treated using a carbon dioxide laser. Out of 495 patients (91.84%) 1 patient was cured, 37 patients (6.86%) required more than one operation to be cured, and in 7 patients (1.30%) the treatment failed.

Developmental and gestational changes of phosphoethanolamine and taurine in rat brain, striated and smooth muscle.

Concentrations of taurine and phosphoethanolamine in rat smooth (intestinal and uterine), skeletal and cardiac muscle, and brain have been determined, using high-performance liquid chromatography (HPLC), to examine possible interrelationships in their tissue content. Concentrations were determined in fetal and neonatal samples, as well as in adult tissue, to investigate whether phosphoethanolamine and taurine levels are influenced by developmental state. The effect of gestational state was also studied. A marked decrease in cerebral phosphoethanolamine concentration during development was found together with a concomitant decrease in striated muscle but not in the two smooth muscles studied. A rise in uterine phosphoethanolamine during the early postpartum period confirmed previous NMR data. This occurred only in the uterus, suggesting it is specific to the process of involution within the myometrium. Taurine concentrations showed no consistent pattern of change with postnatal development. In adult animals, the highest levels of taurine were found in cardiac muscle. Pregnancy was associated with a fall in taurine concentration in all tissues, suggesting an influence of steroid hormones. As taurine is cotransported with Na+ in many systems it may be related to the increased water retention seen in pregnancy. It is concluded that marked changes in phosphoethanolamine and taurine levels occur during development and gestation, but that the changes are not interdependent, i.e., the changes are tissue specific.