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Alternative memory in the CD8 T cell lineage - PubMed

Review

Alternative memory in the CD8 T cell lineage

You Jeong Lee et al. Trends Immunol. 2011 Feb.

Abstract

A prominent population of innate CD8+ T cells develops in the thymus of several gene-deficient mouse strains, including Itk, KLF2, CBP and Id3. These cells have the phenotype and function of memory CD8+ T cells, without previous exposure to antigen. Surprisingly, the cytokine IL-4 plays a key role in their development. As this developmental mechanism was discovered, it came to light that innate CD8+ T cells exist also in normal mice and in humans. In this review, we discuss how these cells develop, compare and contrast them to other CD8 memory cells, and discuss their potential physiological relevance.

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Figures

Figure 1
Figure 1. Innate CD8+ T cells develop via a cell-extrinsic mechanism

(a) Schematic of an “unequal mixed bone marrow chimera” approach wherein bone marrow cells are mixed at skewed ratios and used to reconstitute irradiated host animals. If a cell extrinsic bystander effect exists, wild-type (WT) progenitors in the minority would show a phenotypic change (middle). If the effect is cell intrinsic, gene-deficient (KO) progenitors in the minority would show a phenotypic change (right). These experiments showed innate CD8+ T cells develop via a cell-extrinsic mechanism. (b) NKT cells expand and secrete IL-4 in various gene-deficient mice. This induces wild-type “bystander” CD8 SP T cells to adopt memory phenotype and function. This effect of IL-4 on CD8 T cells is dependent on the transcription factor Eomes.

Figure 2
Figure 2. Various genes act at distinct stages to expand three types of PLZF+ cells

The genes indicated in red regulate the number of PLZF+ γδ NKT (a), αβ iNKT (b), or T-T CD4 T cells (c) in mice. ITK, SLP76, Id3 and CBP likely act downstream of the selection step that initiates γδ NKT development. KLF2 is more likely to regulate the later expansion of NKT, and affects both γδ NKT and αβ iNKT. The CIITAtg creates MHC class II dependent thymocyte-thymocyte (T-T) interactions that generate polyclonal CD4+ T cells expressing PLZF.

Figure 3
Figure 3. Multiple pathways to becoming memory-phenotype cells

a) Conventional memory cells are generated when naïve T cells become primed during infection via recognition of cognate antigens and inflammatory cytokines like IL-12 and IFNγ. Such cells upregulate T-bet and Eomes and facilitate the rapid clearance of pathogens during secondary infection, via cytolysis and production of IFNγ. b) Homeostatic or virtual (unprimed) memory cells are generated when naïve T cells are in lymphopenic conditions and respond to self-antigens and homeostatic cytokines like IL-7. Lymphopenic conditions can be induced by artificial radiation and acute or chronic infection. Such cells produce IFNγ in response to inflammatory cytokines IL-12 and IL-18, and thus could provide non-cognate or innate protection early on in infections. c) Bystander or unprimed memory CD8+ T cells are generated when developing thymocytes respond to elevated IL-4, presumably together with self-antigen. Like homeostatic memory cells, bystander memory cells produce IFNγ in response to inflammatory cytokines and could provide non-cognate or innate protection early during infections. Bystander memory CD8+ T cells upregulate Eomes, but not T-bet, though the functional implications of this are not yet clear.

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References

    1. Lee YJ, et al. MHC class II-dependent T-T interactions create a diverse, functional and immunoregulatory reaction circle. Immunol Cell Biol. 2009;87:65–71. - PubMed
    1. Urdahl KB, et al. Positive selection of MHC class Ib-restricted CD8(+) T cells on hematopoietic cells. Nat Immunol. 2002;3:772–779. - PMC - PubMed
    1. Kumanovics A, et al. Genomic organization of the mammalian MHC. Annu Rev Immunol. 2003;21:629–657. - PubMed
    1. Treiner E, Lantz O. CD1d- and MR1-restricted invariant T cells: of mice and men. Curr Opin Immunol. 2006;18:519–526. - PubMed
    1. Johansson-Lindbom B, Agace WW. Generation of gut-homing T cells and their localization to the small intestinal mucosa. Immunol Rev. 2007;215:226–242. - PubMed

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