Regulatory T cells suppress antigen-driven CD4 T cell reactivity following injury

• Published in: Journal of leukocyte biology Vol. 89; no. 1; pp. 137 - 147
• Main Authors: MacConmara, Malcolm P., Tajima, Goro, OˈLeary, Fionnuala, Delisle, Adam J., McKenna, Ann M., Stallwood, Christopher G., Mannick, John A., Lederer, James A.
• Format: Journal Article
• Language: English
• Published: United States Society for Leukocyte Biology 01.01.2011
• Subjects: Adoptive Transfer; Animals; Antigen-Presenting Cells - immunology; B7-1 Antigen - metabolism; B7-2 Antigen - metabolism; Burns - immunology; Burns - pathology; CARS; CD4 Antigens - immunology; Cell Proliferation; danger‐associated molecular patterns (DAMPs); Dendritic Cells - metabolism; Epitopes - immunology; Host Defense & Pathophysiology; immunization; inflammation; Lymph Nodes - immunology; Lymphocyte Activation - immunology; Macrophages - metabolism; Mice; Mice, Inbred BALB C; Mice, Transgenic; Models, Immunological; SIRS; T-Lymphocytes, Regulatory - cytology; T-Lymphocytes, Regulatory - immunology; Th1 Cells - immunology
• ISSN: 0741-5400; 1938-3673
• DOI: 10.1189/jlb.0210082

Regulatory T cells control the in vivo expansion and response of antigen‐specific CD4 T cell in an injury‐dependent manner. Injury initiates local and systemic host responses and is known to increase CD4 Treg activity in mice and humans. This study uses a TCR transgenic T cell adoptive transfer approach and in vivo Treg depletion to determine specifically the in vivo influence of Tregs on antigen‐driven CD4 T cell reactivity following burn injury in mice. We report here that injury in the absence of recipient and donor Tregs promotes high antigen‐driven CD4 T cell expansion and increases the level of CD4 T cell reactivity. In contrast, CD4 T cell expansion and reactivity were suppressed significantly in injured Treg‐replete mice. In additional experiments, we found that APCs prepared from burn‐ or sham‐injured, Treg‐depleted mice displayed significantly higher antigen‐presenting activity than APCs prepared from normal mice, suggesting that Tregs may suppress injury responses by controlling the intensity of APC activity. Taken together, these findings demonstrate that Tregs can actively control the in vivo expansion and reactivity of antigen‐stimulated, naïve CD4 T cells following severe injury.