Evaluation of the T cells and costimulatory molecules in the protective efficacy of 30 kDa secretory protein against experimental tuberculosis.
Phenotypic changes of T lymphocytes and B7 costimulatory molecules in mice first vaccinated with mycobacterial 30 kDa secretory protein and then challenged with Mycobacterium tuberculosis H37Rv (Group 2) were monitored using flow cytometry and compared with non-vaccinated, but challenged mice (Group 1). In Group 1, the proportion of CD3+ and CD4+ T cells increased until 28 days postinfection (p.i.) and then declined to levels even less than healthy controls (non-vaccinated and non-challenged healthy mice), especially at later stages of infection (i.e. 72 days p.i.). However, the levels of CD8+ T cells did not decline and remained either significantly higher or similar to healthy control levels. In Group 2, however, the levels of CD3+ and CD4+ T cells did not decline as seen in Group 1, but remained significantly higher than in Group 1. Furthermore, the profile of CD8+ T cells remained similar to what was observed in Group 2. In order to elucidate Th1-Th2 bias, the ratio of IgG2a/IgG1 bearing cells was enumerated by flow cytometry. A predominantly Th1 response was observed in Group 1 until 28 days p.i. (IgG2a/IgG1 ratio was >1). However, in Group 2 a predominantly Th1 bias was observed throughout the period studied in terms of IgG2a/IgG1 ratios. The examination of expression of B7-1 and B7-2 costimulatory molecules on a monocyte gated population was carried out. In Group 2, the B7-1 and B7-2 expression was found to be significantly higher compared to Group 1, especially at later stages of infection (i.e. 60 and 72 days p.i.). Thus, these results suggest the capability of mycobacterial 30 kDa secretory protein in restoring the T-cell responses, especially at later stages of infection, possibly by augmentation of both B7-1 and B7-2. Further, these costimulatory molecules are probably required for effective T-cell responses against virulent mycobacterial challenge in a murine model of tuberculosis.
Yadav
D
D
Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Khuller
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G
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology*; D018122:B7-1 Antigen / Q000378:metabolism*; D051940:B7-2 Antigen; D001426:Bacterial Proteins / Q000276:immunology*; D004195:Disease Models, Animal; D005434:Flow Cytometry; D006023:Glycoproteins / Q000276:immunology; D007114:Immunization; D008198:Lymph Nodes / Q000276:immunology; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D013601:T-Lymphocytes / Q000502:physiology*; D014376:Tuberculosis / Q000276:immunology* / Q000517:prevention & control
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D001426:Bacterial Proteins; C497965:Cd86 protein, mouse; D006023:Glycoproteins; D008562:Membrane Glycoproteins