Immunophenotypic characterization of peripheral T lymphocytes in Mycobacterium tuberculosis infection and disease.
The 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.
Rodrigues
D S S
DS
Infectious Diseases Discipline and Immunization Center, Federal University of São Paulo, São Paulo, Brazil.
Medeiros
E A S
EA
Weckx
L Y
LY
Bonnez
W
W
Salomão
R
R
Kallas
E G
EG
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000293:Adolescent; D000328:Adult; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D017493:Leukocyte Common Antigens / Q000032:analysis; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D008297:Male; D008562:Membrane Glycoproteins; D008875:Middle Aged; D009169:Mycobacterium tuberculosis; D009244:NAD+ Nucleosidase / Q000032:analysis; D016176:T-Lymphocyte Subsets / Q000145:classification / Q000276:immunology*; D014397:Tuberculosis, Pulmonary / Q000276:immunology*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000032:analysis
D015703:Antigens, CD; D000943:Antigens, Differentiation; D006684:HLA-DR Antigens; D008562:Membrane Glycoproteins; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D017493:Leukocyte Common Antigens; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1