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.

TLDR

ETA‑1 encodes a highly acidic secreted protein with adhesion‑binding features and maps to the Ric locus on chromosome 5, a region that confers resistance to Rickettsia tsutsugamushi infection. The study describes the murine ETA‑1 cDNA, which is abundantly expressed following T‑cell activation. Inbred mouse strains carrying the Eta‑1a allele were resistant to RT infection, whereas those with Eta‑1b were susceptible, indicating that Eta‑1 mediates genetic resistance and that its strong expression is part of a rapid T‑cell‑dependent response that inhibits early bacterial replication.

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.