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      Intracellular Bacterial Infection and Invariant NKT Cells

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          Abstract

          The invariant (i) natural killer (NK)T cells represent a unique subset of T lymphocytes which express the Vα14 chain of the T cell receptor (TCR), that recognizes glycolipid antigens presented by the nonpolymorphic major histocompatibility complex (MHC) class I-like antigen presentation molecule CD1d, and they participate in protection against some microbial pathogens. Although iNKT cells have originally been regarded as T cells co-expressing NKR-P1B/C (NK1.1: CD 161), they do not seem to consistently express this marker, since NK1.1 surface expression on iNKT cells undergoes dramatic changes following facultative intracellular bacterial infection, which is correlated with functional changes of this cell population. Accumulating evidence suggests that NK1.1 allows recognition of "missing-self", thus controling activation/inhibition of NK1.1-expressing cells. Therefore, it is tempting to suggest that iNKT cells participate in the regulation of host immune responses during facultative intracellular bacterial infection by controlling NK1.1 surface expression. These findings shed light not only on the unique role of iNKT cells in microbial infection, but also provide evidence for new aspects of the NK1.1 as a regulatory molecule on these cells.

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          Most cited references91

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          Immune response in mice that lack the interferon-gamma receptor.

          Interferon-gamma (IFN-gamma) exerts pleiotropic effects, including antiviral activity, stimulation of macrophages and natural killer cells, and increased expression of major histocompatibility complex antigens. Mice without the IFN-gamma receptor had no overt anomalies, and their immune system appeared to develop normally. However, mutant mice had a defective natural resistance, they had increased susceptibility to infection by Listeria monocytogenes and vaccinia virus despite normal cytotoxic and T helper cell responses. Immunoglobulin isotype analysis revealed that IFN-gamma is necessary for a normal antigen-specific immunoglobulin G2a response. These mutant mice offer the possibility for the further elucidation of IFN-gamma-mediated functions by transgenic cell- or tissue-specific reconstitution of a functional receptor.
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            Mouse CD1-specific NK1 T cells: development, specificity, and function.

            NK1 T cells are a specialized population of alpha/beta T cells that coexpress receptors of the NK lineage and have the unique potential to very rapidly secrete large amounts of cytokines, providing early help for effector cells and regulating the Th1 or Th2 differentiation of some immune responses. NK1 T cells express a restricted TCR repertoire made of an invariant TCR alpha chain, V alpha 14-J alpha 281, associated with polyclonal V beta 8, V beta 7, and V beta 2 TCR beta chains. NK1 T cells recognize the products of the conserved family of MHC class I-like CD1 genes, apparently in the absence of foreign antigens. Thus, this novel regulatory pathway, which straddles the innate and the adaptive immune systems, is unique in that its activation may not require associative recognition of antigen. Here, we review the specificity and function of mouse NK1 T cells, and we discuss the relationship of this lineage to mainstream T cells and NK cells.
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              Functionally Distinct Subsets of CD1d-restricted Natural Killer T Cells Revealed by CD1d Tetramer Staining

              CD1d-restricted natural killer (NK)T cells are known to potently secrete T helper (Th)1 and Th2 cytokines and to mediate cytolysis, but it is unclear how these contrasting functional activities are regulated. Using lipid antigen–loaded CD1d tetramers, we have distinguished two subsets of CD1d-restricted T cells in fresh peripheral blood that differ in cytokine production and cytotoxic activation. One subset, which was CD4−, selectively produced the Th1 cytokines interferon γ and tumor necrosis factor α, and expressed NKG2d, a marker associated with cytolysis of microbially infected and neoplastic cells. This subset up-regulated perforin after exposure to interleukin (IL)-2 or IL-12. In contrast, CD4+ CD1d-restricted NKT cells potently produced both Th1 and Th2 cytokines, up-regulated perforin in response to stimulation by phorbol myristate acetate and ionomycin but not IL-2 or IL-12, and could be induced to express CD95L. Further, for both CD1d-restricted NKT cell subsets, we found that antigenic stimulation induced cytokine production but not perforin expression, whereas exposure to inflammatory factors enhanced perforin expression but did not stimulate cytokine production. These results show that the various activities of CD1d-restricted T cells in tumor rejection, autoimmune disease, and microbial infections could result from activation of functionally distinct subsets, and that inflammatory and antigenic stimuli may influence different effector functions.
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                Author and article information

                Journal
                Yonsei Med J
                YMJ
                Yonsei Medical Journal
                Yonsei University College of Medicine
                0513-5796
                1976-2437
                28 February 2009
                24 February 2009
                : 50
                : 1
                : 12-21
                Affiliations
                Laboratory of Immunology, Department of Laboratory Sciences, Gunma University School of Health Sciences, Maebashi, Gunma, Japan.
                Author notes
                Reprint address: requests to Dr. Masashi Emoto, Laboratory of Immunology, Department of Laboratory Sciences, Gunma University School of Health Sciences, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan. Tel: 81-27-220-8935, Fax: 81-27-220-8935, memoto@ 123456health.gunma-u.ac.jp
                Article
                10.3349/ymj.2009.50.1.12
                2649871
                19259343
                169a4f9c-bf46-4e18-886e-b406edcdb1fe
                Copyright © 2009 The Yonsei University College of Medicine

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 04 November 2008
                Categories
                Review Article

                Medicine
                natural killer 1.1,intracellular bacteria,liver,listeria monocytogenes,natural killer t cell,nkr-p1

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