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Deletion of the activating NK cell receptor NKG 2D accelerates rejection of cardiac allografts
Author(s) -
Fabritius Cornelia,
Ritschl Paul Viktor,
Resch Thomas,
Roth Mario,
Ebner Susanne,
Günther Julia,
Mellitzer Vanessa,
Nguyen AnhVu,
Pratschke Johann,
Sauter Martina,
Klingel Karin,
Kotsch Katja
Publication year - 2017
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/ajt.14467
Subject(s) - nkg2d , blockade , medicine , cd8 , transplantation , degranulation , immunology , interferon , receptor , stimulation , cytotoxic t cell , immune system , biology , in vitro , biochemistry
It has already been shown that neutralization of the activating NK cell receptor NKG 2D in combination with co‐stimulation blockade prolongs graft survival of vascularized transplants. In order to clarify the underlying cellular mechanisms, we transplanted complete MHC ‐disparate BALB /c‐derived cardiac grafts into C57 BL /6 wildtypes or mice deficient for NKG 2D (Klrk1 −/− ). Although median survival was 8 days for both recipient groups, we detected already at day 5 posttransplantation significantly greater intragraft frequencies of NK p46 + NK cells in Klrk1 −/− recipients than in wildtypes. This was followed by a significantly greater infiltration of CD 4 + , but a lesser infiltration of CD 8 + T cell frequencies. Contrary to published observations, co‐stimulation blockade with CTLA 4‐Ig resulted in a significant acceleration of cardiac rejection by Klrk1 −/− recipients, and this result was confirmed by applying a neutralizing antibody against NKG 2D to wildtypes. In both experimental setups, grafts derived from Klrk1 −/− recipients were characterized by significantly higher levels of interferon‐γ mRNA , and both CD 4 + and CD 8 + T cells displayed a greater capacity for degranulation and interferon‐γ production. In summary, our results clearly illustrate that NKG 2D expression in the recipient is important for cardiac allograft survival, thus supporting the hypothesis that impairment of NK cells prevents the establishment of graft acceptance.