Generation of cytolytic T cells in individuals infected by Mycobacterium tuberculosis and vaccinated with BCG.

Pithie, Alan; Rahelu, M; Kumararatne, D. S.; Drysdale, P; Gaston, J. S. H.; Iles, P.B.; Innes, John; Ellis, Clare

doi:10.1136/thx.47.9.695

Cited by 27 publications

(19 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although the reasons for the success are not well defined, the use of a live vaccine probably induced the required Type 1 cellularimmune responses and CD8+ CTLs (Flynn etal., 1992). Similar types of immune responses have been observed in BeG-vaccinated humans (Pithie et al, 1992;Mustafa et al, 1993). Unfortunately, the results oflarge BCG vaccine clinical trials have been highly variable; protective immune responses were induced in up to 80% of some test populations whereas insignificant levels of protection were documented in other groups (Smith et aI., 1988;Colditz et al, 1994).…”

Section: Immune Responses Against Intracellular Bacteriasupporting

confidence: 52%

Immunological and Formulation Design Considerations for Subunit Vaccines

Newman

Powell²

1995

Vaccine Design

View full text Add to dashboard Cite

Section: Immune Responses Against Intracellular Bacteriasupporting

confidence: 52%

Immunological and Formulation Design Considerations for Subunit Vaccines

Newman

Powell²

1995

Vaccine Design

View full text Add to dashboard Cite

“…ϩ and CD8 ϩ ) may also be important in the clearance of M. bovis (39,44,47). Together, these studies demonstrate the complexity and redundancy of the host response during tuberculosis as well as potential sites for immune modulation with compounds such as 1,25(OH) 2 …”

mentioning

confidence: 81%

Modulation ofMycobacterium bovis-Specific Responses of Bovine Peripheral Blood Mononuclear Cells by 1,25-Dihydroxyvitamin D₃

Waters¹,

Nonnecke

Rahner³

et al. 2001

Clin Diagn Lab Immunol

View full text Add to dashboard Cite

(48) and Zairians living in Belgium (35) compared to control individuals with less pigmented skin, presumably due to diminished synthesis. Tuberculosis, likewise, is common among individuals with heavily pigmented skin that relocate from equatorial regions to higher latitudes, in part due to deficiencies in vitamin D synthesis within the skin (65). In addition, patients with untreated tuberculosis often have lower concentrations of 25(OH)D 3 in plasma than do healthy subjects, and tuberculosis tends to occur during the winter when exposure to sunlight is reduced and production of cholecalciferol within the skin is diminished (16). Evidence for a clear correlation between vitamin D deficiency and susceptibility to tuberculosis, however, remains controversial. In vitro studies, however, provide more compelling evidence linking vitamin D status to susceptibility to tuberculosis.Addition of 1,25(OH) 2 D 3 to monocyte-macrophage cultures infected with Mycobacterium tuberculosis suppresses bacterial growth and viability (17,53,54). The mechanism of this suppression is mediated, at least partially, by nitric oxide (NO) (53). Induction of inducible NO synthase of macrophages and subsequent generation of reactive nitrogen intermediates (RNI) toxic to mycobacteria is a potent mechanism of killing (14,15,21,22,34). Cytokines (e.g., tumor necrosis factor alpha and gamma interferon [IFN-␥]) from antigen-specific T cells and/or from macrophages stimulated directly with mycobacterial antigens is responsible for RNI-mediated antimycobacterial defense (24,60). Production of RNI is crucial for controlling acute as well as latent infections in the mouse model of virulent M. tuberculosis infection (14,15,25,34). The role of RNI in mycobacterial killing within human macrophages is less clear. Alveolar macrophages of tuberculosis patients express high levels of inducible NO synthase, suggesting a role for RNI in disease pathogenesis and/or host defense (42). Nevertheless, recent evidence suggests that human but not mouse macro-* Corresponding author. Mailing address: United States Department

show abstract

“…Lymphocyte cloning experiments [5] and passive T‐cell transfer [6] have demonstrated the reactive capacity and protective ability of CD4 + cells. This T‐cell activity appears to work via cytotoxicity against infected target cells [7]. The effect is at least partially related to T cell interferon gamma (IFNγ) production in response to M. tuberculosis antigens [8].…”

Section: Introductionmentioning

confidence: 99%

Immunophenotypic characterization of peripheral T lymphocytes inMycobacterium tuberculosisinfection and disease

Rodrigues¹,

Medeiros²,

Weckx

et al. 2002

Clinical and Experimental Immunology

View full text Add to dashboard Cite

SUMMARYThe cellular immune response probably plays a pivotal role in determining the clinical outcome after exposure to Mycobacterium tuberculosis. We used multi-parameter flow-cytometry to evaluate the distribution of T-lymphocyte subsets during infection and disease caused by M. tuberculosis. Samples were obtained from 71 volunteers to identify the T CD4 + and CD8 + lymphocyte numbers, and the activation plus memory/naïve phenotypes, as defined by CD38, HLA-DR, CD45RA and CD27 markers. Subjects were divided into 18 healthy volunteers without detectable reaction to purified protein derivative (PPD -), 18 health care workers with a recent conversion to PPD, 20 patients with active pulmonary tuberculosis (TBC) and 15 patients with treated TBC at 6 months of therapy. By multiple-comparison analyses, the T CD4 + lymphocyte number of the TBC group was lower than the PPD -group (P < 0·05). This difference was apparently lost after treatment. The higher and the lower number of naïve T CD4 + cells was observed in the PPD -and TBC group, respectively. CD8 + T lymphocytes were also statistically different among the four groups (P = 0·0002), lower in the TBC group (P < 0·05). CD8 + T lymphocyte activation was evaluated by the CD38 and HLA-DR surface expression. The percentage distribution of these markers was statistically different between the four groups (P = 0·0055). TBC patients had a higher percentage of CD38 + cells and mean fluorescence index, suggesting an overall increase of cell activation. These results suggest that peripheral T lymphocytes reflect cellular activation during TBC, along with possible redistribution of naïve, memory/effector and late differentiated memory/effector phenotypes in the peripheral blood after infection and disease caused by M. tuberculosis.

show abstract

Generation of cytolytic T cells in individuals infected by Mycobacterium tuberculosis and vaccinated with BCG.

Abstract: Background Macrophage activation by cytokines provides only a partial explanation of antimycobacterial immunity in man. Because cytolytic T lymphocytes

Cited by 27 publications

References 25 publications

Immunological and Formulation Design Considerations for Subunit Vaccines

Immunological and Formulation Design Considerations for Subunit Vaccines

Modulation ofMycobacterium bovis-Specific Responses of Bovine Peripheral Blood Mononuclear Cells by 1,25-Dihydroxyvitamin D₃

Immunophenotypic characterization of peripheral T lymphocytes inMycobacterium tuberculosisinfection and disease

Contact Info

Product

Resources

About

Generation of cytolytic T cells in individuals infected by Mycobacterium tuberculosis and vaccinated with BCG.

Abstract: Background Macrophage activation by cytokines provides only a partial explanation of antimycobacterial immunity in man. Because cytolytic T lymphocytes

Cited by 27 publications

References 25 publications

Immunological and Formulation Design Considerations for Subunit Vaccines

Immunological and Formulation Design Considerations for Subunit Vaccines

Modulation ofMycobacterium bovis-Specific Responses of Bovine Peripheral Blood Mononuclear Cells by 1,25-Dihydroxyvitamin D3

Immunophenotypic characterization of peripheral T lymphocytes inMycobacterium tuberculosisinfection and disease

Contact Info

Product

Resources

About

Modulation ofMycobacterium bovis-Specific Responses of Bovine Peripheral Blood Mononuclear Cells by 1,25-Dihydroxyvitamin D₃