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Limited recognition of Mycobacterium tuberculosis-infected macrophages by polyclonal CD4 and CD8 T cells from the lungs of infected mice
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Limited recognition of Mycobacterium tuberculosis-infected macrophages by polyclonal CD4 and CD8 T cells from the lungs of infected mice
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Journal Article
Limited recognition of Mycobacterium tuberculosis-infected macrophages by polyclonal CD4 and CD8 T cells from the lungs of infected mice
2020
Overview
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.
Publisher
Elsevier Inc,Nature Publishing Group US,Elsevier Limited
Subject
/ Animals
/ Antigens
/ Antigens, Bacterial - immunology
/ Bacillus Calmette-Guerin vaccine
/ Bacterial Proteins - immunology
/ BCG
/ Biomedical and Life Sciences
/ CD4-Positive T-Lymphocytes - immunology
/ CD8-Positive T-Lymphocytes - immunology
/ Enzyme-linked immunosorbent assay
/ Enzyme-Linked Immunospot Assay
/ Epitopes
/ Humans
/ Interferon-gamma - metabolism
/ Major histocompatibility complex
/ Mice
/ Mycobacterium bovis - immunology
