TCR-mediated target cell lysis by CD4+NK1+ liver T lymphocytes

Abstract

In the liver, an unusual T lymphocyte population exists with the intriguing phenotype CD4+NK1+ TCRαβ(int). Thus far, functions of these lymphocytes remained elusive. Recently, however, CD4+NK1+ liver T lymphocytes have been shown to produce cytokines. Here we show that sorted CD4+NK1+ liver lymphocytes from naive mice lyse target cells after TCRαβ or CD3, but not TCRγδ, engagement. Liver lymphocytes from β2-microglobulin-deficient gene disruption mutant mice failed to express such cytolytic activities and in vivo treatment with anti-NK1.1 mAb or anti-CD4 mAb, but not anti-CD8 mAb, markedly reduced target cell lysis. In vivo administration of rIL-12 impaired TCRαβ-mediated target cell lysis by liver lymphocytes. A similar down-regulation of cytolytic activities was observed with liver lymphocytes from mice infected with Listeria monocytogenes or Mycobacterium bovis BCG, which are potent IL-12 inducers. We anticipate (i) that cytolytic CD4+NK1+ T lymphocytes contribute to immunosurveillance of inflammatory processes in the liver and (ii) that they are influenced by IL-12.