A subset of neutrophils in human systemic inflammation inhibits T cell responses through Mac-1.

By J. Pillay, V. Kamp, E. van Hoffen, T. Visser, T. Tak, J. Lammers, L. Ulfman, L. Leenen, P. Pickkers, L. Koenderman. Journal of Clinical Investigation, 2012

815 citations recorded by the source corpus.

Suppression of immune responses is necessary to limit damage to host tissue during inflammation, but it can be detrimental in specific immune responses, such as sepsis and antitumor immunity. Recently, immature myeloid cells have been implicated in the suppression of immune responses in mouse models of cancer, infectious disease, bone marrow transplantation, and autoimmune disease. Here, we report the identification of a subset of mature human neutrophils (CD11cbright/CD62Ldim/CD11bbright/CD16bright) as what we believe to be a unique circulating population of myeloid cells, capable of suppressing human T cell proliferation. These cells were observed in humans in vivo during acute systemic inflammation induced by endotoxin challenge or by severe injury. Local release of hydrogen peroxide from the neutrophils into the immunological synapse between the neutrophils and T cells mediated the suppression of T cell proliferation and required neutrophil expression of the integrin Mac-1 (αMβ2). Our data demonstrate that suppression of T cell function can be accomplished by a subset of human neutrophils that can be systemically induced in response to acute inflammation. Identification of the pivotal role of neutrophil Mac-1 and ROS in this process provides a potential target for modulating immune responses in humans.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/2b91645bad71885825bc354d68f8ece1e4142018

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In Immunology

1. C. Rosales
2. A. Mócsai
3. C. Lowell
4. T. Mayadas
5. X. Cullere

Citations in the corpus

• Neutrophil: A Cell with Many Roles in Inflammation or Several Cell Types? (2018, background): “Also, they are capable of inhibiting T lymphocytes by direct cell contact involving the integrin Mac1, and by local delivery of reactive oxygen species (ROS) (Pillay et al., 2012).”
• The Multifaceted Functions of Neutrophils (2013, background): “More recently, a subset of neutrophils was shown to inhibit T cell proliferation by releasing ROS in the immunological synapse (165).”
• Diverse novel functions of neutrophils in immunity, inflammation, and beyond (2013, background): “A subset of human neutrophils also inhibits T cell responses during acute systemic inflammatory reactions such as bacterial sepsis (Pillay et al., 2012).”
• Neutrophils: Between Host Defence, Immune Modulation, and Tissue Injury (2015, background): “Importantly, in systemic inflammation, a distinct subset of activated CD62L neutrophils was found to suppress T cell proliferation mediated through a Mac-1-dependent mechanism [114].”