Immunogenicity of dormancy-related antigens in individuals infected with Mycobacterium tuberculosis in Japan

Abstract

T-cell responses to six antigens might contribute to natural protection against dormant M. tuberculosis. These antigens are therefore considered to be potential targets of novel vaccines to control M. tuberculosis reactivation in the Japanese population.

Multifunctional T Cell Response to DosR and Rpf Antigens Is Associated with Protection in Long-Term Mycobacterium tuberculosis-Infected Individuals in Colombia

“…Thus, our observations may suggest that mono-and bifunctional CD4 ϩ and CD8 ϩ T cells producing IFN-␥ and/or TNF-␣ can contribute to effective mycobacterial growth control in individuals with LTBI (34, 48,64). Although in other studies higher frequencies of mono-and bifunctional CD4 ϩ T cells producing IFN-␥ and/or TNF-␣ in response to RD1 were found in PTB, compared to LTBI (18,19,27,28), the difference in the lengths of the in vitro cultures might explain this difference. Short-term cultures (24 h) have been mainly associated with the detection of a T cell effector memory phenotype, while long-term cultures (5 to 7 days), as used in this study, have been mainly associated with the detection of a T central memory phenotype (25,36,56,57,64).…”

“…Statistical differences between the groups were calculated with the Mann-Whitney U test. *, P Ͻ 0.05; **, P Ͻ 0.01; ***, P Ͻ 0.001. in response to in vitro stimulation with ESAT6 and CFP10; as discussed above, however, results have been inconclusive (15)(16)(17)(18)(19)(20).…”

“…A higher frequency of multifunctional CD4 ϩ T cells, producing IFN-␥, TNF-␣, and IL-2, in peripheral blood mononuclear cells (PBMCs) from patients with active pulmonary tuberculosis (PTB), compared to individuals with latent TB infection (LTBI), was reported (15)(16)(17) and decreased following anti-TB treatment (16,17). However, others observed a lower frequency of multifunctional T cells in PTB, compared to LTBI (18)(19)(20), which increased after anti-TB treatment (18,19). Furthermore, an increase in the frequency of bifunctional CD4 ϩ T cells producing IFN-␥ and IL-2 was reported for PTB patients after anti-TB therapy (11).…”

“…Recent studies demonstrated that RD1 antigen stimulation induces greater proportions of multifunctional CD4 ϩ T cells in individuals with LTBI, compared to patients with active TB (18)(19)(20). In this study, we found that mono-and bifunctional CD4 ϩ and CD8 ϩ T cells producing IFN-␥ and/or TNF-␣ were observed more frequently than monofunctional IL-2 ϩ or multifunctional (IFN-␥ ϩ TNF-␣ ϩ IL-2 ϩ ) T cells, independent of the antigen and disease status, as observed by others (48).…”

Mycobacterium tuberculosis DosR Regulon Gene Rv2004c Encodes a Novel Antigen with Pro-inflammatory Functions and Potential Diagnostic Application for Detection of Latent Tuberculosis

“…Transposon site hybridization mutation studies showed that Rv2004c is essential for the survival of Mtb in murine macrophages (23). The immunogenic potential of Rv2004c in latent tuberculosis infected (LTBI) individuals of Japanese population was reported (24). But, studies about humoral immune response in LTBI individuals from high burden countries such as India are lacking.…”