Inborn errors of human interferon gamma (IFN-gamma) immunity underlie mycobacterial disease. We report a patient with mycobacterial disease due to inherited deficiency of the transcription factor T-bet. The patient has extremely low counts of circulating Mycobacterium-reactive natural killer (NK), invariant NKT (iNKT), mucosal-associated invariant T (MATT), and V delta 2(+) gamma delta T lymphocytes, and of Mycobacterium-non reactive classic T(H)1 lymphocytes, with the residual populations of these cells also producing abnormally small amounts of IFN-gamma. Other lymphocyte subsets develop normally but produce low levels of IFN-gamma, with the exception of CD8(+) alpha beta T and non-classic CD4(+) cep T(H)1* lymphocytes, which produce IFN-gamma normally in response to mycobacterial antigens. Human T-bet deficiency thus underlies mycobacterial disease by preventing the development of innate (NK) and innate-like adaptive lymphocytes (iNKT, MATT, and V delta 2(+) gamma delta T cells) and IFN-gamma production by them, with mycobacterium-specific, IFN-gamma-producing, purely adaptive CD8(+) alpha beta T and CD4(+) alpha beta T(H)1* cells unable to compensate for this deficit.
Human T-bet governs innate and innate-like IFN-gamma immunity against mycobacteria / Yang, R., Mele, F., Worley, L., Langlais, D., Rosain, J., Benhsaien, I., Elarabi, H., Croft, C.a., Doisne, J., Zhang, P., Weisshaar, M., Jarrossay, D., Latorre, D., Shen, Y., Han, J., Gruber, C., Markle, J., Al Ali, F., Rahman, M., Khan, T., et al.. - In: CELL. - ISSN 0092-8674. - 183:7(2020), pp. 1826-1847.e31. [10.1016/j.cell.2020.10.046]
Human T-bet governs innate and innate-like IFN-gamma immunity against mycobacteria
Latorre D;
2020-01-01
Abstract
Inborn errors of human interferon gamma (IFN-gamma) immunity underlie mycobacterial disease. We report a patient with mycobacterial disease due to inherited deficiency of the transcription factor T-bet. The patient has extremely low counts of circulating Mycobacterium-reactive natural killer (NK), invariant NKT (iNKT), mucosal-associated invariant T (MATT), and V delta 2(+) gamma delta T lymphocytes, and of Mycobacterium-non reactive classic T(H)1 lymphocytes, with the residual populations of these cells also producing abnormally small amounts of IFN-gamma. Other lymphocyte subsets develop normally but produce low levels of IFN-gamma, with the exception of CD8(+) alpha beta T and non-classic CD4(+) cep T(H)1* lymphocytes, which produce IFN-gamma normally in response to mycobacterial antigens. Human T-bet deficiency thus underlies mycobacterial disease by preventing the development of innate (NK) and innate-like adaptive lymphocytes (iNKT, MATT, and V delta 2(+) gamma delta T cells) and IFN-gamma production by them, with mycobacterium-specific, IFN-gamma-producing, purely adaptive CD8(+) alpha beta T and CD4(+) alpha beta T(H)1* cells unable to compensate for this deficit.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
