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Published on: December 27, 2016
Glutamine requirement of proliferating T lymphocytes
1Department of Biochemistry, University of Oxford, United Kingdom.
Insights
Glutamine significantly impacts lymphocyte activation by influencing interleukin-2 (IL-2) production, IL-2 receptor expression, and transferrin receptor expression, suggesting a crucial early role.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Glutamine is essential for lymphocyte proliferation, but its precise mechanism of action remains unclear.
- Understanding glutamine's role is vital for modulating immune responses.
Purpose of the Study:
- To investigate the effect of glutamine on critical lymphocyte activation events.
- To determine if glutamine influences interleukin-2 (IL-2) production, IL-2 utilization, IL-2 receptor expression, and transferrin receptor expression.
Main Methods:
- Spleen lymphocytes from rats or mice were cultured with concanavalin A (Con A) and varying glutamine concentrations.
- Key activation markers including IL-2 production, IL-2 receptor, and transferrin receptor expression were quantified.
- IL-2 utilization was assessed using an IL-2-dependent cell line.
Main Results:
- Increased glutamine concentrations correlated with higher IL-2 production (up to 39-fold increase).
- Glutamine availability enhanced IL-2 receptor and transferrin receptor expression on lymphocytes.
- Lymphocyte IL-2 utilization was directly dependent on glutamine levels in the culture medium.
Conclusions:
- All investigated lymphocyte activation components (IL-2 production, IL-2 use, IL-2 receptor expression, transferrin receptor expression) are glutamine-dependent.
- Glutamine likely plays a significant role in the early stages of lymphocyte activation, potentially acting as an initial signaling molecule.
Abstract:
Glutamine is required for lymphocyte proliferation but the site of glutamine action is not yet known. In this study, the effect of glutamine on key events that occur during lymphocyte activation [interleukin-2 (IL-2) production, IL-2 use, IL-2 receptor expression, transferrin receptor expression] was investigated. Rat or mouse spleen lymphocytes were cultured in the presence of the T-cell mitogen concanavalin A (Con A) and various concentrations of glutamine. There was a trend (not significant) for the ratio of CD4+:CD8+ spleen lymphocytes to increase (from 1.9 to 2.6) as the concentration of glutamine in culture medium increased from 0 to 2 mmol/L. As the concentration of glutamine increased, there was an increase in the proportion of cells expressing the IL-2 receptor (from 30 to 45%) and the transferrin receptor (from 34% to 55%). As the concentration of glutamine increased there was a 2.7-fold increase in the concentration of IL-2 in the culture medium. The IL-2 concentration was decreased when an IL-2 receptor-blocking antibody was included in the culture medium; the IL-2 concentrations measured were taken to indicate the initial Con A-stimulated production of IL-2. In these conditions, the IL-2 concentration in the medium increased 39-fold as the glutamine concentration increased. The use of IL-2 by an IL-2-dependent cell line was dependent on the glutamine concentration in the culture medium. Thus, all four components of lymphocyte activation investigated (IL-2 production, IL-2 use, IL-2 receptor expression, transferrin receptor expression) were dependent on the concentration of glutamine present in the culture medium. Thus, glutamine might provide an early signal in the lymphocyte activation process.
