Structural and functional studies of the early T lymphocyte activation 1 (Eta-1) gene. Definition of a novel T cell-dependent response associated with genetic resistance to bacterial infection.

Abstract

We describe a murine cDNA, designated Early T lymphocyte activation 1 (ETA-1) which is abundantly expressed after activation of T cells. Eta-1 encodes a highly acidic secreted product having structural features of proteins that bind to cellular adhesion receptors. The Eta-1 gene maps to a locus on murine chromosome 5 termed Ric that confers resistance to infection by Rickettsia tsutsugamushi (RT), an obligate intracellular bacterium that is the etiological agent for human scrub typhus. With one exception, inbred mouse strains that expressed the Eta-1a allele were resistant to RT infection (RicR), and inbred strains expressing the Eta-1b allele were susceptible (RicS). These findings suggest that Eta-1 is the gene inferred from previous studies of the Ric locus (5). Genetic resistance to RT infection is associated with a strong Eta-1 response in vivo and inhibition of early bacterial replication. Eta-1 gene expression appears to be part of a surprisingly rapid T cell-dependent response to bacterial infection that may precede classical forms of T cell-dependent immunity.

Implication of allelic polymorphism of osteopontin in the development of lupus nephritis in MRL/lpr mice

“…Thus, we selected OPN as a candidate gene for its polymorphisms and its relationship to immune responses. Prior to this study, the Opn product, termed the early T lymphocyte activation 1 (Eta-1) or secreted phosphoprotein 1 (Spp1), had been known for its cytokine activities affecting migration of macrophages to an inflammatory site [14] and polyclonal B cell activation and differentiation [10,15]. With respect to autoimmune disease, Patarca et al [16] reported dysregulated expression of Eta-1 in a T lymphocyte subset (CD4 -CD8 -) during the development of autoimmune disease in MRL/lpr mice.…”

“…It should be noted that these substitutions may affect some of the functional sites of OPN. Indeed, the Tyr 261 and the Asp 172 correspond to a heparin binding site and a phosphorylation site overlapped by the homologous Itga 4 b 1 binding site of fibronectin, respectively [15]. Asn 126 neighbors the RGDS motif that serves as a binding site for Itga v b 1 [36], a v b 3 [37], and a v b 5 [38].…”

“…Responder cells used in each assay were from MRL/+ mice and C3H/+ mice to avoid the effect of high intrinsic production of OPN by lpr immunocytes, possibly due to dysregulated expression in CD4 -/CD8 -lymphocytes [15].…”

Elevation of osteopontin levels in brain tumor cells reduces burden and promotes survival through the inhibition of cell dispersal

“…Osteopontin was initially identified as a protein secreted by malignant epithelial cells [14,25,32,33]. It is constitutively secreted in diverse tissues and inducible in T-lymphocytes, epidermal cells, bone, macrophages and tumor cells of various origins [11,16,23,36].…”

L’ostéopontine, une molécule aux multiples facettes

“…Cependant, il semble que la fonction de l'OPN dans la maladie soit plus complexe puisque, in vitro, elle est paradoxalement un facteur Production par les cellules immunocompétentes Au cours de ces pathologies immunologiques ou infectieuses, l'OPN est surtout sécrétée par les cellules macrophagiques [49] et histiocytaires. Son expression a éga-lement été rapportée à la phase précoce de l'activation des lymphocytes T, d'où son autre nom « eta-1 » (early T cell activation factor gene 1) [50]. Dans les lymphocytes T humains, l'OPN est spécifiquement surexprimée dans la sous-population TH1, pro-inflammatoire, et non dans la population TH2 [51], suggérant son implication dans les pathologies médiées par l'inflammation TH1.…”