Unconventional NK1.1 intermediate TCR cells as major T lymphocytes expanding in chronic graft-versus-host disease

Abstract

Chronic graft‐versus‐host disease (GVHD) accompanying autoimmune disease was induced in (C57BL/6×DBA/2) F1 mice (H‐2b/d) by an injection of splenic T cells of parental DBA/2 origin (H‐2d). In parallel with the onset of proteinuria, an expansion of lymphocytes was induced in the liver and kidney, showing a peak at 2 weeks after the onset of disease. The majority of lymphocytes were of recipient origin (H‐2b/d). The main lymphocyte subset among T cells at the pre‐onset stage and after the onset of disease was CD8+ NK1.1– CD3int cells (of extrathymic, hepatic origin) in both the liver and kidney. NK1.1– CD3int cells confer primarily neither NK‐like nor NKT‐like cytotoxicity. No induction of these types of cytotoxicity was observed in these mice with the expansion of NK1.1– CD3int cells. This raised the possibility that granulocytes induced in the liver and kidney might be associated with tissue damage. The present results suggest that, similarly to the case of autoimmune‐prone mice with genetic background (e.g. MRL‐lpr/lpr mice and BXSB mice), NK1.1– CD3int cells of extrathymic, hepatic origin might be crucial lymphocytes involved in the induction of the autoimmune‐like disease in mice with chronic GVHD, in conjunction with Bcells (e.g. B‐1 cells).

Role of α-adrenergic stimulus in stress-induced modulation of body temperature, blood glucose and innate immunity

“…Hepatic lymphocytes were prepared as previously described [17]. Briefly, the liver was pressed through 200-gauge stainless steel mesh and suspended in Eagle's MEM medium supplemented with 5 mM HEPES and 2% FCS.…”

Expansion of NK1.1- intermediate TCR cells and granulocytes in mice trans-planted with TAP-1-deficient cells

“…We previously reported that NK1.1 − CD3 int cells sometimes induced the activation of granulocytes via their production of IFNγ, TNFα, or GM-CSF (i.e., inflammatory cytokines) (15,19). This possibility was also examined in these experiments (Fig.…”

“…In sharp contrast, allogeneic cytotoxicity was induced in the liver of mice which had undergone allogeneic BMT. ) is known to accompany the activation of granulocytes (15,19), parameters of granulocytes were examined in parallel. It was found that there was a prominent expansion of granulocytes in both the liver and spleen at the fulminant stage.…”

“…In addition to NK cells, other primordial lymphocytes have been characterized as components of innate immunity. Such cells include natural killer T cells (NKT cells) (13,21,22) (18,19,32). NKT cells are generated through an alternative pathway in the thymus and home to the liver (5-7, 10, 11), whereas NK1.1 − TCR int cells are generated extrathymically in the liver.…”

Monoclonal auto-antibodies and sera of autoimmune patients react with Plasmodium falciparum and inhibit its in vitro growth

“…NK1.1 -�CR int cell activation is associated with the proliferation of auto-antibody-producing B1 cells and protection against the infection (Yoder & Goodrum 2001, Kanda et al 2010. Because a similar mechanism has been shown to occur in certain murine AID states (Miyakawa et al 2002, Kawabe et al 2004) and because there is an increase of unconventional � cells with NK markers in malaria patients' blood (Watanabe et al 2003), the production of auto-Ab during the course of plasmodia infections and some AID could overlap with pathways that are necessary for the development of malarial protection.…”