Depletion of a γδ T Cell Subset Can Increase Host Resistance to a Bacterial Infection

Abstract

γδ T lymphocytes have been shown to regulate immune responses in diverse experimental systems. Because distinct γδ T cell subsets, as defined by the usage of certain TCR V genes, preferentially respond in various diseases and disease models, we have hypothesized that the various γδ T cell subsets carry out different functions. To test this, we compared one particular γδ T cell subset, the Vγ1+ subset, which represents a major γδ T cell type in the lymphoid organs and blood of mice, to other subsets and to γδ T cells as a whole. Using Listeria monocytogenes infection as an infectious disease model, we found that bacterial containment improves in mice depleted of Vγ1+ γδ T cells, albeit mice lacking all γδ T cells are instead impaired in their ability to control Listeria expansion. Our findings indicate that Vγ1+ γδ T cells reduce the ability of the innate immune system to destroy Listeria, even though other γδ T cells as a whole promote clearance of this pathogen.

MHC class I-dependent Vγ4+pulmonary T cells regulate αβ T cell-independent airway responsiveness

“…This finding is consistent with other recent studies associating TCR-defined subsets of ␥␦ T cells with distinct functional roles (23,(25)(26)(27)(28). The requirement for a TCR-defined population also suggests that TCR-ligand recognition and the particular specific ligand of the regulatory ␥␦ T cell subset are important in maintaining normal airway function (29).…”

Delineation of the Function of a Major γδ T Cell Subset during Infection

“…Although the identity and means by which specific populations of ␥␦ T cells normally protect the host from immune-mediated tissue injury as a consequence of infection have not been identified, the reported anti-inflammatory and antibacterial activities of V␥1 ϩ T cells (24,36) suggest that they may perform such a role. This possibility was investigated further in this study by determining whether V␥1 ϩ T cells contribute to pathogen containment and eradication and/or can prevent the liver necrosis seen in Lm-infected TCR␦ Ϫ/Ϫ mice.…”

“…V␥1 ϩ T cells are prominent during the early stages of Lm infection, in which they have been shown to constitutively express IL-12Rs (30) and to be major producers of IFN-␥ (17,30), consistent with an early proinflammatory role and with acting as a bridge between the innate and adaptive immune systems. However, studies of the overall protective role of V␥1 ϩ T cells in Lm infection are inconclusive, with in vivo depletion studies resulting in either increased (35) or decreased (36) bacterial numbers, leaving it unclear whether bacterial containment and protection are properties of the V␥1 ϩ or other ␥␦ T cell subsets.…”

Diversity of γδ T-cell antigens

“…58,[60][61][62][63] In a study with human cd T cells, live bacteria were required to elicit responses of cd T cells in vitro. A cd T cell line derived from such culture responded specifically to the large LLO-derived peptide LLO 470-508.…”