Regulation of Activated CD4+ T Cells by NK Cells Via the Qa-1-NKG2A Inhibitory Pathway

Overview

Journal Immunity

Publisher Cell Press

Specialty Allergy & Immunology

Date 2007 May 19

PMID 17509909

Citations 124

Authors

Linrong Lu

Koichi Ikizawa

Dan Hu

Miriam B F Werneck

Kai W Wucherpfennig

Harvey Cantor

Affiliations

Soon will be listed here.

Abstract

The ability of natural-killer cells to regulate adaptive immunity is not well understood. Here we define an interaction between the class Ib major histocompatibility complex (MHC) molecule Qa-1-Qdm on activated T cells responsible for adaptive immunity and CD94-NKG2A inhibitory receptors expressed by natural-killer cells by using Qa-1-deficient and Qa-1 knockin mice containing a point mutation that selectively abolishes Qa-1-Qdm binding to CD94-NKG2A receptors. The Qa-1-NKG2A interaction protected activated CD4+ T cells from lysis by a subset of NKG2A+ NK cells and was essential for T cell expansion and development of immunologic memory. Antibody-dependent blockade of this Qa-1-NKG2A interaction resulted in potent NK-dependent elimination of activated autoreactive T cells and amelioration of experimental autoimmune encephalomyelitis. These findings extend the functional reach of the NK system to include regulation of adaptive T cell responses and suggest a new clinical strategy for elimination of antigen-activated T cells in the context of autoimmune disease and transplantation.

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