Over a decade ago, several reports in the literature demonstrated the expression of T cell receptor (TCR) αβ and γδ in cells of the myeloid lineage. Puellmann et al. (2006) reported a small fraction of neutrophils in the peripheral blood of healthy individuals expressing TCRα and β chains, while also detecting neutrophils expressing TCRγ- and δ-ligand binding subunits. Such results were later supported by Legrand et al. (2009) who provided evidence for the expression of TCRγδ on eosinophil granulocytes from healthy individuals, while Beham et al. (2011) described that subpopulations of monocytes also express TCRαβ, which were not limited to blood monocytes, but were also detected in tissue macrophages. Adapting the term TCR-like receptor, Fuchs et al. (2012) demonstrated that in neutrophils TCRαβ is expressed throughout the entire life span and declines in old age, which was also proposed as a novel mechanism of immune senescence in neutrophils. Such receptors were also detected in macrophages in atherosclerosis lesions (Fuchs et al., 2012) and tumor microenvironments (Fuchs et al., 2015).

Similarly, Beham et al. (2011) showed that TCRαβ bearing macrophages accumulate at the inner host-pathogen contact zone of caseous granulomas from patients with lung tuberculosis and uncover the role of tumor necrosis factor (TNF)-regulated TCRαβ expression in granuloma formation. By the same token, TCRβ expression in neutrophils correlated with parasite burden and enhanced phagocytosis during plasmodium berghei ANKA malaria infection (Chorazeczewski et al., 2018, Oakley et al., 2018).

Such observations, except from overthrowing the dogma about the exclusive expression of TCRs in T cells, they also raise questions about the exclusion of TCRαβ and γδ expression in the same T cell. In an attempt to shed light to these observations, the present study concentrated on the macrophage cell line RAW 264.7, which, because of its origin and the cell purity, could provide definite information as to the ectopic expression of TCRs.

The RAW 264.7 cell line consists of monocyte/macrophage-like cells and was established from the ascites of a tumor-induced male BAB/14 mouse by intraperitoneal injection with the Abelson murine leukemia virus (Raschke et al., 1978). BAB/14 mice are congenics for the immunoglobulin heavy chain linkage group of C57BL/6 on BALB/c (Blomberg et al., 1972). The RAW 264.7 cells have been described as a model for macrophages, since they are capable of performing pinocytosis and phagocytosis, while upon LPS stimulation they increase nitric oxide (NO) production and enhance phagocytosis (Taciak et al., 2018). Among a systematic expression analysis of 28 genes, CD11b, CD14, Ireb‐2, transferrin receptor (TfR), CD36, iNOS, CD11c, vascular endothelial growth factor receptor 2 (VEGFR2), tartrate‐resistant acidic phosphatase (TRAP), T‐cell immunoglobulin and mucin domain 2 (TIM-2) and hypoxia inducible factor 2a (HIF-2a) were found to have an increasing expression up to passage No. 50. By the same token, CD86, HIF‐1α, CD11a, CD18, CD206, CD200R, Glucose transporter 1 (Glut1) and Ly6c and TfR2, Arg1 and scavenger receptor class A member 5 (SCARA‐5b) showing stable and fluctuating expression respectively, were associated with macrophage activation (Taciak et al., 2018). Furthermore, these cells are able to kill target cells by antibody dependent cytotoxicity (Fuentes et al., 2014), while Lv et al. (2017) were able to polarize RAW 264.7 to M1- and M2-type macrophages by galectin-9. Additionally, these cells express FcγRI and FCγRII/III/IV in a ratio 3:7 which is 10-times lower than the J774 mouse macrophage-model cell line (Verma et al., 2009). RAW 264.7 cells are increasingly used as a cellular model of osteoclastogenic studies (Kong et al., 2019).

Based on the macrophage nature of RAW264.7 cells the present study concentrated on the ectopic expression of TCRs and therefore examined the expression of TCRαβ, TCRγδ, CD3ζ, CD3ε along with the expression of CD4, CD8 and major histocompatibility complex (MHC) class II molecules, in order to evaluate their dual ability to act as antigen presenting cells (APCs) and T cells with or without stimulation of the FCγRII/III receptor by a recombinant CH2-domain of the IgG2a heavy chain (rIgG2aCH2).