Extralymphocytic flexible immune recognition: a new angle on inflammation and aging

Abstract

Longstanding immunological dogma holds that flexible immune recognition, which forms the mechanistic basis of adaptive immunity, is strictly confined to the lymphocyte lineage. In higher vertebrates, flexible immune recognition is represented by recombinatorial antigen receptors of enormous diversity known as immunoglobulins, expressed by B lymphocytes, and the T cell receptor (TCR), expressed by T lymphocytes. The recent discovery of recombinatorial immune receptors that are structurally based on the TCR (referred to as TCR-like immunoreceptors, "TCRL") in myeloid phagocytes such as neutrophils and monocytes/macrophages now challenges the lymphocentric paradigm of flexible immunity. Here, we introduce the emerging concept of "extralymphocytic flexible immune recognition" and discuss its implications for inflammation and aging.

Keywords: TCR; immunosenescence; macrophage; neutrophil.

Figure 1.

Circulating human neutrophils and monocytes express αβT cell receptor-like recombinatorial immune receptors (TCRLαβ). The confocal fluorescence immunocytochemistry images show ∼5–8% subpopulations of circulating neutrophils (left) and monocytes (right) that express the TCRLαβ (arrows). TCRLαβ positive neutrophils and monocytes display yellow and red fluorescence, respectively. Nuclei are counterstained in the left image (blue). CD15⁺ and CD14⁺ purified peripheral blood neutrophils and monocytes, respectively, were isolated from representative healthy donors and immunostained using antibodies against the TCRαβ (yellow, neutrophils; red; monocytes). Monoytes were costained for MHC-II (green). Adapted from Puellmann et al. [9] and Beham et al. [13].

Figure 2.

TCRL expression in phagocytes. The V(D)J recombined TCRL variable chains (α-δ) that have thus far been identified in each phagocyte population are indicated. The existence of TCRL extends the cellular basis for flexible immune recognition in jawed vertebrates beyond T cells and provides a molecular platform for extralymphocytic flexible immune recognition. This diagram was adopted from a previous publication [25].

Figure 3.

Conccurrent decline of the capacities for phagocytosis and flexible immune recognition in myeloid phagocytes during aging. The myeloid machinery for flexible immune recognition is based on the recently identified recombinatorial TCRL. This process is paralleled by the decline of the T cell receptor (TCR) in the lymphoid lineage.