Limited recognition of Mycobacterium tuberculosis-infected macrophages by polyclonal CD4 and CD8 T cells from the lungs of infected mice

Immune responses following Mycobacterium tuberculosis (Mtb) infection or vaccination are frequently assessed by measuring T-cell recognition of crude Mtb antigens, recombinant proteins, or peptide epitopes. We previously showed that not all Mtb-specific T cells recognize Mtb-infected macrophages. Th...

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Bibliographic Details
Published in:Mucosal immunology 2020-01, Vol.13 (1), p.140-148
Main Authors: Patankar, Yash R, Sutiwisesak, Rujapak, Boyce, Shayla, Lai, Rocky, Lindestam Arlehamn, Cecilia S, Sette, Alessandro, Behar, Samuel M
Format: Article
Language:English
Subjects:
Animals
Antigens
Antigens, Bacterial - immunology
Bacillus Calmette-Guerin vaccine
Bacterial Proteins - immunology
BCG
CD4 antigen
CD4-Positive T-Lymphocytes - immunology
CD8 antigen
CD8-Positive T-Lymphocytes - immunology
Cell recognition
Cells, Cultured
Enzyme-linked immunosorbent assay
Enzyme-Linked Immunospot Assay
Epitopes
ESAT-6 antigen
Humans
Immunity (Disease)
Infections
Interferon-gamma - metabolism
Lung - immunology
Lymphocytes
Lymphocytes T
Macrophages
Macrophages - immunology
Macrophages - microbiology
Major histocompatibility complex
Mice
Mice, Inbred C57BL
Multiplicity of infection
Mycobacterium bovis - immunology
Mycobacterium tuberculosis
Mycobacterium tuberculosis - physiology
Tuberculosis
Tuberculosis - immunology
Vaccination
γ-Interferon
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Summary:Immune responses following Mycobacterium tuberculosis (Mtb) infection or vaccination are frequently assessed by measuring T-cell recognition of crude Mtb antigens, recombinant proteins, or peptide epitopes. We previously showed that not all Mtb-specific T cells recognize Mtb-infected macrophages. Thus, an important question is what proportion of T cells elicited by Mtb infection recognize Mtb-infected macrophages. We address this question by developing a modified elispot assay using viable Mtb-infected macrophages, a low multiplicity of infection and purified T cells. In C57BL/6 mice, CD4 and CD8 T cells were classically MHC restricted. Comparable frequencies of T cells that recognize Mtb-infected macrophages were determined using interferon-γ elispot and intracellular cytokine staining, and lung CD4 T cells more sensitively recognized Mtb-infected macrophages than lung CD8 T cells. Compared to the relatively high frequencies of T cells specific for antigens such as ESAT-6 and TB10.4, low frequencies of total pulmonary T cells elicited by aerosolized Mtb infection recognize Mtb-infected macrophages. Finally, we demonstrate that BCG vaccination elicits T cells that recognize Mtb-infected macrophages. We propose that the frequency of T cells that recognize infected macrophages could correlate with protective immunity and may be an alternative approach to measuring T-cell responses to Mtb antigens.
ISSN:1933-0219
1935-3456
DOI:10.1038/s41385-019-0217-6