Dihydrolipoamide dehydrogenase-Lpd (Rv0462)-specific T cell recall responses are higher in healthy household contacts of TB: a novel immunodominant antigen from M. tuberculosis

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

Raja, Alamelu¹ 

[1] Department of Immunology, National Institute for Research in Tuberculosis, Chennai, India

关键词: latent/active tuberculosis;    whole blood culture;    multicolor flow cytometry;    antigens;    immunostaining;   

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

The partial effectiveness against pulmonary tuberculosis (PTB), displayed by the existing tuberculosis (TB) vaccine, bacillus Calmette-Guérin (BCG), highlights the need for novel vaccines to replace or improve BCG. In TB immunology, antigen-specific cellular immune response is frequently considered indispensable. Latency-associated antigens are intriguing as targets for TB vaccine development. The mycobacterial protein, dihydrolipoamide dehydrogenase (Lpd; Rv0462), the third enzyme of the pyruvate dehydrogenase (PDH) complex, facilitates Mycobacterium tuberculosis to resist host reactive nitrogen intermediates. Multicolor flow cytometry analysis of whole-blood cultures showed higher Lpd-specific Th1 recall response (IFN-γ, TNF-α, and IL-2; P = 0.0006) and memory CD4⁺ and CD8⁺ T cells (CCR7⁺ CD45RA⁻ and CCR7⁻ CD45RA⁻) in healthy household contacts (HHC) of TB (P < 0.0001), which is comparable with or higher than the standard antigens, ESAT-6 and CFP-10. The frequency of Lpd-specific multifunctional T cells was higher in HHC compared with PTB patients. However, there is no significant statistical correlation. Regulatory T cell (T_reg) analysis of HHCs and active TB patients demonstrated very low Lpd-specific CD4⁺ T_regs relative to ESAT-6 and CFP-10. Our study demonstrates that the Lpd antigen induces a strong cellular immune response in healthy mycobacteria-infected individuals. In consideration of this population having demonstrated immunologic protection against active TB disease development, our data are encouraging about the possible use of Lpd as a target for further TB subunit vaccine development.

【 授权许可】

CC BY