Elsevier

Molecular Immunology

Volume 42, Issue 4, February 2005, Pages 451-454
Molecular Immunology

Review
NK cell regulation of T cell-mediated responses

https://doi.org/10.1016/j.molimm.2004.07.025Get rights and content

Abstract

NK cells promote adaptive immune responses through their production of type 1 and type 2 cytokines or chemokines. Secretion of these factors by activated NK cells influences the differentiation of B and T lymphocytes. Increasing evidence indicates that NK cells are also directly involved in dendritic cell (DC) maturation. By contrast, a potential role for direct cell–cell interactions between NK and T lymphocytes, in particular CD4+ T cells, has not been explored. We provide evidence that activated human NK cells are able of promoting TcR-dependent proliferation of resting autologous peripheral blood CD4+ T cells by a process that involves costimulatory molecules of the immunoglobulin (Ig) and tumor necrosis factor (TNF) superfamilies. These findings suggest a novel link between natural and adaptative immune responses.

Section snippets

NK cell regulation of T cell-mediated responses through the production of cytokines, chemokines, and interactions with DC

NK cells promote adaptive immune responses through their production of type 1 and type 2 cytokines or chemokines. Following viral infections, the NK cell production of IFN-γ plays a key role in the initial antiviral response, for example by activating macrophages to secrete IL-12 that is crucial for the differentiation of T cell into Th1 effectors and for the development of CD8+ cytotoxic cells (Biron et al., 1999, French and Yokoyama, 2003). After murine cytomegalovirus (MCMV) infection, IFN-γ

Expression of costimulatory ligands on activated NK cells allow direct interactions with T cells

Previously, NK cells have been assumed to participate in adaptive immune responses by an indirect mechanism that involves their secretion of cytokines or chemokines in response to stimulation by pro-inflammatory cytokines or interferons produced by myeloid cells or non-hematopoietic cells due to infection with pathogens. However, there is emerging data suggesting the possibility that activated NK cells might also communicate directly with T cells by a process involving cognate cell–cell

Acknowledgments

L.L.L. is an American Cancer Society Research Professor and A.Z. was a recipient of an American–Italian Cancer Foundation Fellowship and of a research contract with the University of Rome “La Sapienza”. These studies were supported by NIH grant CA89294 and a grant from A.I.R.C. to A.S.

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