| Autor: |
Oja AE; Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory , Amsterdam , Netherlands., Vieira Braga FA; Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory , Amsterdam , Netherlands., Remmerswaal EB; Department of Experimental Immunology, Academic Medical Center, Amsterdam, Netherlands; Renal Transplant Unit, Division of Internal Medicine, Academic Medical Centre, Amsterdam-Zuidoost, Netherlands., Kragten NA; Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory , Amsterdam , Netherlands., Hertoghs KM; Department of Experimental Immunology, Academic Medical Center , Amsterdam , Netherlands., Zuo J; College of Medical and Dental Sciences, Institute of Immunology and Immunotherapy, University of Birmingham , Edgbaston, Birmingham , UK., Moss PA; College of Medical and Dental Sciences, Institute of Immunology and Immunotherapy, University of Birmingham , Edgbaston, Birmingham , UK., van Lier RA; Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory , Amsterdam , Netherlands., van Gisbergen KP; Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Amsterdam, Netherlands; Department of Experimental Immunology, Academic Medical Center, Amsterdam, Netherlands., Hombrink P; Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory , Amsterdam , Netherlands. |
| Abstrakt: |
The T cell lineage is commonly divided into CD4-expressing helper T cells that polarize immune responses through cytokine secretion and CD8-expressing cytotoxic T cells that eliminate infected target cells by virtue of the release of cytotoxic molecules. Recently, a population of CD4 + T cells that conforms to the phenotype of cytotoxic CD8 + T cells has received increased recognition. These cytotoxic CD4 + T cells display constitutive expression of granzyme B and perforin at the protein level and mediate HLA class II-dependent killing of target cells. In humans, this cytotoxic profile is found within the human cytomegalovirus (hCMV)-specific, but not within the influenza- or Epstein-Barr virus-specific CD4 + T cell populations, suggesting that, in particular, hCMV infection induces the formation of cytotoxic CD4 + T cells. We have previously described that the transcription factor Homolog of Blimp-1 in T cells (Hobit) is specifically upregulated in CD45RA + effector CD8 + T cells that arise after hCMV infection. Here, we describe the expression pattern of Hobit in human CD4 + T cells. We found Hobit expression in cytotoxic CD4 + T cells and accumulation of Hobit + CD4 + T cells after primary hCMV infection. The Hobit + CD4 + T cells displayed highly overlapping characteristics with Hobit + CD8 + T cells, including the expression of cytotoxic molecules, T-bet, and CX3CR1. Interestingly, γδ + T cells that arise after hCMV infection also upregulate Hobit expression and display a similar effector phenotype as cytotoxic CD4 + and CD8 + T cells. These findings suggest a shared differentiation pathway in CD4 + , CD8 + , and γδ + T cells that may involve Hobit-driven acquisition of long-lived cytotoxic effector function. |
