Natural Killer Cells Recognize Friend Retrovirus-Infected Erythroid Progenitor Cells through NKG2D–RAE-1 Interactions In Vivo

Ogawa, Tatsuya; Tsuji-Kawahara, Sachiyo; Yuasa, Takae; Kinoshita, Saori; Chikaishi, Tomomi; Takamura, Shiki; Matsumura, Haruo; Seya, Tsukasa; Sakurai, Toshihiko; Miyazawa, Masaaki

doi:10.1128/jvi.02146-10

Cited by 19 publications

(19 citation statements)

References 52 publications

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“…Various NKG2D ligands have been characterized in mice, including Rae1 and MULT1 [64]. Many different viruses have been shown to induce up-regulation of NKG2D ligands on infected cells in mice and humans [5,[65][66][67]. NKG2DL has also been shown to be relevant in influenza; in-vitro infection of human dendritic cells led to up-regulation of NKG2DL on the infected cells [68].…”

Section: Cd8mentioning

confidence: 99%

Influenza infection results in local expansion of memory CD8+ T cells with antigen non-specific phenotype and function

Sckisel

Tietze

Zamora

et al. 2013

Clinical and Experimental Immunology

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Summary Primary viral infections induce activation of CD8+ T cells responsible for effective resistance. We sought to characterize the nature of the CD8 + T cell expansion observed after primary viral infection with influenza. Infection of naive mice with different strains of influenza resulted in the rapid expansion of memory CD8 + T cells exhibiting a unique bystander phenotype with significant up-regulation of natural killer group 2D (NKG2D), but not CD25, on the CD44 high CD8+ T cells, suggesting an antigen non-specific phenotype. We further confirmed the non-specificity of this phenotype on ovalbuminspecific (OT-I) CD8 + T cells, which are not specific to influenza. These nonspecific CD8 + T cells also displayed increased lytic capabilities and were observed primarily in the lung. Thus, influenza infection was shown to induce a rapid, antigen non-specific memory T cell expansion which is restricted to the specific site of inflammation. In contrast, CD8 + T cells of a similar phenotype could be observed in other organs following administration of systemic agonistic anti-CD40 and interleukin-2 immunotherapy, demonstrating that bystander expansion in multiple sites is possible depending on whether the nature of activation is either acute or systemic. Finally, intranasal blockade of NKG2D resulted in a significant increase in viral replication early during the course of infection, suggesting that NKG2D is a critical mediator of anti-influenza responses prior to the initiation of adaptive immunity. These results characterize further the local bystander expansion of tissue-resident, memory CD8 + T cells which, due to their early induction, may play an important NKG2D-mediated, antigen non-specific role during the early stages of viral infection.

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Section: Cd8mentioning

confidence: 99%

Influenza infection results in local expansion of memory CD8+ T cells with antigen non-specific phenotype and function

Sckisel

Tietze

Zamora

et al. 2013

Clinical and Experimental Immunology

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“…Results from several research groups largely agree on the role of virus-neutralizing antibodies and CD4 ϩ T cells in immune control of FV infection (6)(7)(8)(9)(10)(11)(12)(13)(14)(15). Natural killer cells also contribute to FV elimination and are essential for vaccine-induced protection of highly susceptible mice (8,16). However, there are conflicting views on the role of CD8 ϩ T cells in FV control.…”

mentioning

confidence: 99%

Elimination of Friend Retrovirus in the Absence of CD8⁺T Cells

Tsuji-Kawahara

Miyazawa

2014

J Virol

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Friend retrovirus complex (FV) induces acute erythroid cell hyperplasia and massive splenomegaly followed by the emergence of fatal erythroleukemia upon inoculation into adult mice of susceptible strains (1-3). Because the disease can progress in the presence of host immune responses, FV has served as a useful model to study how retroviruses evade immune control (1,3,4). Depending on genotypes at several host loci, some strains of mice can eliminate virus-producing cells and recover from splenomegaly, while others progress rapidly to fatal pathology (1,3,5). Results from several research groups largely agree on the role of virus-neutralizing antibodies and CD4 ϩ T cells in immune control of FV infection (6-15). Natural killer cells also contribute to FV elimination and are essential for vaccine-induced protection of highly susceptible mice (8, 16). However, there are conflicting views on the role of CD8 ϩ T cells in FV control. Earlier studies associated major histocompatibility complex class I (MHC-I) alleles with spontaneous recovery from FVinduced splenomegaly, and FV-specific, CD8ϩ cytotoxic T cells were detected (1, 5). Further, the recovery in H2 b mice was abrogated when CD8 ϩ T cells were depleted (6). On the other hand, by using FV-encoded epitopes recognized by CD4 ϩ T cells as peptide vaccines, we have shown that highly susceptible (BALB/c ϫ C57BL/6)F 1 mice can still be protected from FV challenge and eliminate virus-producing cells in the absence of CD8 ϩ T cells (9). Interestingly, MHC-I genotypes influenced cytokine production from CD4 ϩ T cells upon FV infection (17, 18), indicating the possible indirect role of CD8 ϩ T cells. C57BL/6 (B6) mice lack the expression of a short form of hematopoietic cell-specific receptor tyrosine kinase, Stk, and do not develop FV-induced erythroid cell proliferation (19). Some reports have indicated that CD8 ϩ T cells are essential in controlling FV infection in B6 mice, as infectious centers at an early time point after FV infection increased upon depletion of CD8 ϩ T cells (20)(21)(22). However, infectious centers were detected in the above-described reports with monoclonal antibody 720 (23) that reacts only with the helper component of FV, Friend murine leukemia virus (F-MuLV), but not with the pathogenic component, the spleen focus-forming virus (SFFV). In our recent work (24), SFFV was eliminated from B6 mice by 2 weeks after infection, and CD8 ϩ T cell-deficient B6 mice remained resistant to FV-induced disease development. Thus, the increase of F-MuLV infectious centers after CD8 ϩ T cell depletion, albeit statistically significant, may not reflect pathologically significant changes in SFFV load.Here, we examined changes in SFFV copy numbers in CD8 ϩ T cell-deficient B6 mice after FV infection. CD8 ϩ T cell-deficient B6 mice nevertheless eliminated both F-MuLV and SFFV proviruses, though more slowly than the wild-type B6 mice did, as shown in Fig. 1. Thus, while CD8 ϩ T cells do contribute to control FV infection, they are not essential for the elimination o...

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“…The expansion of TER-119 ϩ erythroid progenitor cells in the spleen with high level expression of F-MuLV gp70 and SFFV gp55, the progressive increase in the numbers of F-MuLV and SFFV proviral integrations in the spleen cell genome, and oligoclonal integration of both F-MuLV and SFFV proviruses in the late stage of infection all agree with the previously described cellular and molecular characteristics of FVinduced erythroleukemia that develops in Fv2 s -possessing susceptible mice (2,38), although the tempos of disease development were much slower in CD4 ϩ T cell-deficient B6 mice than in Fv2 spossessing mice. In fact, Fv2 r/s CB6F 1 mice develop significant splenomegaly by 2 weeks after FV infection (27,43) and severe polycythemia at as early as 3 weeks post FV infection (60), while spleen weights of CD4 ϩ T cell-deficient B6 mice at 2 weeks after FV infection were not different from those of infected WT B6 mice (data not shown). Nevertheless, the frequent involvement of the Ets-family PU.1 and Fli1 genes as SFFV integration sites indicates that the fatal leukemia observed in CD4 ϩ T cell-deficient B6 mice, despite the lack of the Fv2 s allele, resembles authentic FV-induced erythroleukemia that emerges through the insertional activation of the transcription factors in proliferating erythroid cells (3,39,45).…”

Section: Discussionmentioning

confidence: 94%

“…As SFFV expanded in Fv2 r B6 mice in the absence of CD4 ϩ T cells but SFFV-infected cells and SFFV proviruses were undetectable or barely detectable at 2 weeks after FV infection in both WT and B cell-deficient B6 mice, it is possible that cellular, but not humoral, immune responses under the control of CD4 ϩ T cells may be required for early elimination of SFFV-infected cells. In fact, it has been shown that NK cells are required for immune control of FV-induced disease development that is brought about by priming CD4 ϩ T cells with a peptide vaccine (24), and NK cells directly recognize and control the expansion of FV-infected erythroid cells (43). Therefore, to explore the presumable roles of cytotoxic effector cells on the elimination of SFFV-infected cells, we administered Ab specific to asialoGM1, CD8, or both to B cell-deficient B6 mice and depleted the numbers of NK and/or CD8 ϩ cells.…”

Section: Fv Infection But B6 Mice Lacking Cd4mentioning

confidence: 99%

“…NK cells were depleted as described previously (24,43). Briefly, rabbit antiserum specific for mouse asialo-ganglio-Ntetraosylceramide (asialoGM1) and control normal rabbit serum were purchased from Wako Pure Chemicals (Osaka, Japan), and the IgG fraction was concentrated by precipitation with 45% (final concentration) ammonium sulfate.…”

Section: Virus and Inoculationmentioning

confidence: 99%

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Differential Requirements of Cellular and Humoral Immune Responses forFv2-Associated Resistance to Erythroleukemia and for Regulation of Retrovirus-Induced Myeloid Leukemia Development

Tsuji-Kawahara

Kawabata

Matsukuma

et al. 2013

J Virol

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Natural Killer Cells Recognize Friend Retrovirus-Infected Erythroid Progenitor Cells through NKG2D–RAE-1 Interactions In Vivo

Cited by 19 publications

References 52 publications

Influenza infection results in local expansion of memory CD8+ T cells with antigen non-specific phenotype and function

Influenza infection results in local expansion of memory CD8+ T cells with antigen non-specific phenotype and function

Elimination of Friend Retrovirus in the Absence of CD8⁺T Cells

Differential Requirements of Cellular and Humoral Immune Responses forFv2-Associated Resistance to Erythroleukemia and for Regulation of Retrovirus-Induced Myeloid Leukemia Development

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Natural Killer Cells Recognize Friend Retrovirus-Infected Erythroid Progenitor Cells through NKG2D–RAE-1 Interactions In Vivo

Cited by 19 publications

References 52 publications

Influenza infection results in local expansion of memory CD8+ T cells with antigen non-specific phenotype and function

Influenza infection results in local expansion of memory CD8+ T cells with antigen non-specific phenotype and function

Elimination of Friend Retrovirus in the Absence of CD8+T Cells

Differential Requirements of Cellular and Humoral Immune Responses forFv2-Associated Resistance to Erythroleukemia and for Regulation of Retrovirus-Induced Myeloid Leukemia Development

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Elimination of Friend Retrovirus in the Absence of CD8⁺T Cells