Cutting Edge: l-Arginine Transfer from Antigen-Presenting Cells Sustains CD4 + T Cell Viability and Proliferation

Metabolomics analyses suggest changes in amino acid abundance, particularly l-arginine (L-ARG), occur in patients with tuberculosis. Immune cells require L-ARG to fuel effector functions following infection. We have previously described an L-ARG synthesis pathway in immune cells; however, its role i...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2022-02, Vol.208 (4), p.793-798
Main Authors: Crowther, Rebecca R, Schmidt, Stephanie M, Lange, Shannon M, McKell, Melanie C, Robillard, Michelle C, Zhao, Junfang, Haffey, Wendy D, Wyder, Michael A, Greis, Kenneth D, Setchell, Kenneth D R, Qualls, Joseph E
Format: Article
Language:English
Subjects:
Animals
Antigen-Presenting Cells - immunology
Antigen-Presenting Cells - metabolism
Arginine - biosynthesis
Arginine - metabolism
Argininosuccinic Aciduria - etiology
Argininosuccinic Aciduria - metabolism
Biological Transport
Biomarkers
CD4-Positive T-Lymphocytes - immunology
CD4-Positive T-Lymphocytes - metabolism
Cell Proliferation
Cell Survival - immunology
Flow Cytometry
Immunophenotyping
Lymphocyte Activation - genetics
Lymphocyte Activation - immunology
Mice
Mice, Transgenic
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Summary:Metabolomics analyses suggest changes in amino acid abundance, particularly l-arginine (L-ARG), occur in patients with tuberculosis. Immune cells require L-ARG to fuel effector functions following infection. We have previously described an L-ARG synthesis pathway in immune cells; however, its role in APCs has yet to be uncovered. Using a coculture system with mycobacterial-specific CD4 T cells, we show APC L-ARG synthesis supported T cell viability and proliferation, and activated T cells contained APC-derived L-ARG. We hypothesize that APCs supply L-ARG to support T cell activation under nutrient-limiting conditions. This work expands the current model of APC-T cell interactions and provides insight into the effects of nutrient availability in immune cells.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.2100652