T cell responses to DosR and Rpf proteins in actively and latently infected individuals from Colombia.
Mycobacterium tuberculosis DosR regulon-encoded proteins elicit strong immune T-cell responses in individuals with latent tuberculosis (LTBI). Also, resuscitation (Rpf) proteins can induce such responses. However, variations in the immunogenicity of the DosR and Rpf proteins have been observed in European and African populations, and no data are published from other geographic areas. In Colombian LTBI and patients with recently diagnosed PTB, we therefore studied the immune response to DosR, Rpf, stress, and nominal antigens from Mtb, in 7-day stimulated cultures. Three DosR (Rv1737c, Rv2029c, Rv2628c) and 2 Rpf (Rv0867 and Rv2389c) antigens were recognized most prominently on the basis of the net IFNγ production (DosR) or the percentage of responding individuals (Rpf). Results show that the selected DosR antigens induced a higher proportion of CD4-T cells producing IFNγ from LTBI, compared to pulmonary TB patients (PTB), while there were no differences in the proportion of CD8-T cells. An increased frequency of CD4, but not CD8 T-cells with a CD45RO(+)CD27(+) phenotype was observed in LTBI in response to Rv2029c, Rv0867c, and Rv2389c, compared to PTB. The levels of cytokines and chemokines in the supernatants of stimulated cells, showed that the DosR and Rpf antigens induced higher levels of IFNγ in cultures from LTBI compared to PTB, although the induced pattern of cytokines and chemokines was also antigen dependent. In summary, our results are consistent with the significant immunogenicity of Mtb DosR and Rpf antigens in LTBI individuals, and confirm and extend previously reported data from other TB affected human populations.
Grupo de Inmunología Celular e Inmunogenética, Instituto de Investigaciones Médicas, Facultad de Medicina, Universidad de Antioquia, Carrera 53 #61-30, Medellín, Colombia.
Felipe
F
Riaño
Leonar
L
Arroyo
Sara
S
París
Mauricio
M
Rojas
Annemieke H
AH
Friggen
Krista E
KE
van Meijgaarden
Kees L M C
KL
Franken
Tom H M
TH
Ottenhoff
Luis F
LF
García
Luis F
LF
Barrera
D000293:Adolescent; D000328:Adult; D000368:Aged; D000942:Antigens, Bacterial / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology*; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D018925:Chemokines / Q000096:biosynthesis; D003105:Colombia; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology*; D004268:DNA-Binding Proteins; D005260:Female; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis; D055985:Latent Tuberculosis / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology; D011494:Protein Kinases / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014397:Tuberculosis, Pulmonary / Q000276:immunology*; D055815:Young Adult
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D018925:Chemokines; D016207:Cytokines; D004268:DNA-Binding Proteins; C542863:DosR protein, Mycobacterium tuberculosis; C113704:resuscitation-promoting factor, bacteria; D007371:Interferon-gamma; D011494:Protein Kinases