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At least 127 records · Page 7Linked to original sources
PubMed1999

Cytokine/chemokine cascades in immunity to tuberculosis.

The relationship between acquired specific resistance and delayed-type hypersensitivity (DTH) in immunity to tuberculosis has long been a topic of debate. Here, Ian Orme and Andrea Cooper propose that the events are separate mechanisms; protection is cytokine driven and initially controls the infection, whereas DTH is primarily chemokine driven and functions to wall off the infection and prevent further dissemination.

Animals↗
PubMed2006

Intramuscular immunization with a monogenic plasmid DNA tuberculosis vaccine: Enhanced immunogenicity by electroporation and co-expression of GM-CSF transgene.

Plasmid DNA vaccine has been widely explored for tuberculosis immunization but there is a need to develop the ways to improve its immunogenicity. In this study, we have constructed a plasmid DNA vaccine coding for Ag85A alone or for both Ag85A and GM-CSF and investigated the immune adjuvant effects of electroporation and GM-CSF co-expression, alone or in combination, on CD4 and CD8 T cell IFN-gamma responses, CTL activities and immune protection from pulmonary Mycobacterium tuberculosis challenge in a Balb/c mouse model. We have found that use of electroporation allows a single intramuscular (i.m.) DNA injection to be as effective as repeated i.m. DNA injections in activation of both Ag85A-specific CD4 and CD8 T cells. Co-expression of immune-enhancing cytokine GM-CSF by the same plasmid DNA TB vaccine could further enhance T cell activation including CTL activities on top of electroporation. With regard to immune protection from pulmonary M. tb challenge, use of electroporation also allows a single i.m. DNA injection to be as effective as repeated i.m. DNA injections. Co-expression of GM-CSF transgene also moderately enhances immune protection and such effect is more evident for systemic protection. However, GM-CSF expression has little added effect on immune protection by electroporation-aided immunization protocols. Our findings thus will help with the development of future DNA TB immunization strategies.

Adjuvants, Immunologic↗
PubMedDate not supplied

Different cytokine production and effector/memory dynamics of alpha beta+ or gamma delta+ T-cell subsets in the peripheral blood of patients with active pulmonary tuberculosis.

Immunity to M.tuberculosis (MTB) infection consists of interactions between various T-cell subsets that control the infection and prevent further reactivation. We analysed the effector/memory T-cell dynamics and cytokines production in the peripheral blood of patients with pulmonary tuberculosis (TB). We observed that the frequency of CD4+ T-cell effectors was significantly increased during active TB, confirming a major role of this T-cell subset in TB immunity. Pre-terminally differentiated CD8+ T-lymphocytes were increased in the peripheral blood as well. In contrast, we observed a reduced number of effector mycobacteria-reactive gammadelta+ T-lymphocytes with a specific defects in reacting to mycobacterial nonpeptidic antigens, suggesting that this innate response is rapidly lost during TB infection. Nevertheless, the frequency of gammadelta+ T-cells effectors in TB patients was higher than the alphabeta+ T-cell response to peptide from MTB-ESAT-6 protein and quantitatively similar to PPD reactivity. Thus, alphabeta+ and gammadelta+ T-cell differentiation and function are differently triggered by active TB infection.

Adult↗
PubMed2004

Effect of vitamin D3 on phagocytic potential of macrophages with live Mycobacterium tuberculosis and lymphoproliferative response in pulmonary tuberculosis.

Immune responses are elicited through antigen presentation and recognition by macrophages and T-lymphocytes, respectively. The immunomodulatory effect of vitamin D(3) on macrophage phagocytic potential with live Mycobacterium tuberculosis, spontaneous and M. tuberculosis culture filtrate antigen induced lymphocyte responses were studied in pulmonary tuberculosis patients (PTBPs) ( n = 31) and normal healthy subjects (NHSs) ( n = 43). Vitamin D(3) at a concentration of 10(-7) M significantly enhanced the macrophage phagocytosis of live M. tuberculosis in normal subjects with low phagocytic potential (less than 10%) ( p = 0.015). No such increase was observed in PTBPs. Vitamin D(3) significantly decreased the spontaneous lymphoproliferative response ( p = 0.022) and increased the apoptosis of peripheral blood mononuclear cells in PTBPs ( p = 0.024). In normals, vitamin D(3) increased the spontaneous lymphoproliferative response. An inverse correlation between macrophage phagocytosis and spontaneous response was observed in NHSs, whereas a direct correlation was seen between vitamin D(3)-treated cells in normal subjects under in vitro condition. Vitamin D(3) decreased the M. tuberculosis culture filtrate antigen induced lymphocyte response significantly in normal subjects ( p = 0.0003), while it had no influence on the lymphocyte response in PTBPs. The present study suggests that exposure to vitamin D(3) increases the phagocytic potential and spontaneous lymphoproliferative response but brings down the antigen-induced response in normals. In tuberculosis, addition of vitamin D(3) has no significant effect on antigen-induced lymphoproliferative response. This may be due to the unresponsive nature of the cells to the action of vitamin D(3) by virtue of the disease, which renders them inactive.

Apoptosis↗
PubMed2006

The live Mycobacterium tuberculosis phoP mutant strain is more attenuated than BCG and confers protective immunity against tuberculosis in mice and guinea pigs.

The Mycobacterium tuberculosis phoP mutant strain SO2 has previously been shown to have reduced multiplication in mouse macrophages and in vivo using the mouse intravenous-infection model. In this study we demonstrate that the M. tuberculosis SO2 is highly attenuated when compared with the parental M. tuberculosis MT103 strain and also more attenuated than BCG in severe combined immunodeficiency disease (SCID) mice. Complementation of the M. tuberculosis SO2 with the wild-type phoP gene restored the virulence of the strain in the SCID mice, confirming that the attenuated phenotype is due to the phoP mutation. In Balb/c mice subcutaneously vaccinated with either M. tuberculosis SO2 or BCG, the proportions of CD4+ and CD8+ populations measured in the spleen were significantly higher in the M. tuberculosis SO2 vaccinated group. In addition, the proportion of antigen-stimulated CD4+/CD8+ cells expressing IFN-gamma was significantly higher in the M. tuberculosis SO2 vaccinated group when compared with the BCG group. Balb/c mice subcutaneously vaccinated with the M. tuberculosis SO2 strain were also protected against intra-venous challenge with M. tuberculosis H37Rv at levels comparable to mice vaccinated with BCG, as measured by reduced bacterial counts in lung and spleens. Guinea pigs subcutaneously vaccinated with the M. tuberculosis SO2 strain were protected against aerosol challenge with M. tuberculosis H37Rv delivered at different doses. A high dose aerosol challenge of M. tuberculosis SO2 vaccinated guinea pigs resulted in superior levels of protection when compared with BCG vaccination, as measured by guinea pig survival and reduction in disease severity in the lung.

Animals↗
PubMed1986

Crossprotection against nontuberculous mycobacterial infections by Mycobacterium tuberculosis memory immune T lymphocytes.

Adoptive immunization of T cell-deficient recipient mice with M. tuberculosis-specific memory immune T lymphocytes conferred upon these animals the ability to express significantly enhanced resistance both to the homologous infection, and to three strains of nontuberculous mycobacteria. These results support the hypothesis, therefore, that antigenic determinants possessed by the four mycobacterial strains that are relevant to the generation of protective cellular immunity are identical or closely crossreactive.

Air Microbiology↗