DOI: 10.4049/jimmunol.163.6.3202. Selective Retention of Activated CD8+ T Cells by the Normal Liver

Selective Retention of Activated CD8+ T Cells by the Normal Liver
10.4049/jimmunol.163.6.3202
Crossref journal-article
Oxford University Press (OUP)
The Journal of Immunology (286)
Abstract
AbstractActivation-induced cell death resulting in peripheral deletion of CD8+ T cells is associated with the accumulation of large numbers of apoptotic T cells in the liver. The hypothesis that this accumulation results from the intrahepatic trapping of T cells from the circulating pool predicts that the liver should retain T cells, which subsequently undergo apoptosis. Here we test this prediction. Perfusion of the liver with lymphocyte mixtures showed retention of activated, but neither resting nor apoptosing, T cells. This trapping was selective for CD8+ cells and was mediated primarily by ICAM-1 constitutively expressed on sinusoidal endothelial cells and Kupffer cells. T cells trapped in the liver became apoptotic. The normal liver is therefore a “sink” for activated T cells.
Bibliography
Mehal, W. Z., Juedes, A. E., & Crispe, I. N. (1999). Selective Retention of Activated CD8+ T Cells by the Normal Liver. The Journal of Immunology, 163(6), 3202â3210.
Authors 3
Wajahat Z. Mehal (first)
Amy E. Juedes (additional)
I. Nicholas Crispe (additional)
References 52 Referenced 195
Dates
Type	When
Created	2 years, 8 months ago (Dec. 31, 2022, 10:28 a.m.)
Deposited	8 months ago (Jan. 2, 2025, 1:06 p.m.)
Indexed	1 week, 4 days ago (Aug. 27, 2025, 12:25 p.m.)
Issued	25 years, 11 months ago (Sept. 15, 1999)
Published	25 years, 11 months ago (Sept. 15, 1999)
Published Print	25 years, 11 months ago (Sept. 15, 1999)
Funders 0
None
BibTeX
@article{Mehal_1999, title={Selective Retention of Activated CD8+ T Cells by the Normal Liver}, volume={163}, ISSN={1550-6606}, url={http://dx.doi.org/10.4049/jimmunol.163.6.3202}, DOI={10.4049/jimmunol.163.6.3202}, number={6}, journal={The Journal of Immunology}, publisher={Oxford University Press (OUP)}, author={Mehal, Wajahat Z. and Juedes, Amy E. and Crispe, I. Nicholas}, year={1999}, month=sep, pages={3202–3210} }
JSON
{
  "indexed": {
    "date-parts": [
      [
        2025,
        8,
        27
      ]
    ],
    "date-time": "2025-08-27T16:25:06Z",
    "timestamp": 1756311906949,
    "version": "3.32.0"
  },
  "reference-count": 52,
  "publisher": "Oxford University Press (OUP)",
  "issue": "6",
  "content-domain": {
    "domain": [],
    "crossmark-restriction": false
  },
  "published-print": {
    "date-parts": [
      [
        1999,
        9,
        15
      ]
    ]
  },
  "abstract": "<jats:title>Abstract</jats:title><jats:p>Activation-induced cell death resulting in peripheral deletion of CD8+ T cells is associated with the accumulation of large numbers of apoptotic T cells in the liver. The hypothesis that this accumulation results from the intrahepatic trapping of T cells from the circulating pool predicts that the liver should retain T cells, which subsequently undergo apoptosis. Here we test this prediction. Perfusion of the liver with lymphocyte mixtures showed retention of activated, but neither resting nor apoptosing, T cells. This trapping was selective for CD8+ cells and was mediated primarily by ICAM-1 constitutively expressed on sinusoidal endothelial cells and Kupffer cells. T cells trapped in the liver became apoptotic. The normal liver is therefore a \u201csink\u201d for activated T cells.</jats:p>",
  "DOI": "10.4049/jimmunol.163.6.3202",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2022,
        12,
        31
      ]
    ],
    "date-time": "2022-12-31T15:28:27Z",
    "timestamp": 1672500507000
  },
  "page": "3202-3210",
  "source": "Crossref",
  "is-referenced-by-count": 195,
  "title": "Selective Retention of Activated CD8+ T Cells by the Normal Liver",
  "prefix": "10.1093",
  "volume": "163",
  "author": [
    {
      "given": "Wajahat Z.",
      "family": "Mehal",
      "sequence": "first",
      "affiliation": [
        {
          "name": "Section of Immunobiology, Yale School of Medicine, New Haven, CT 06520"
        }
      ]
    },
    {
      "given": "Amy E.",
      "family": "Juedes",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Section of Immunobiology, Yale School of Medicine, New Haven, CT 06520"
        }
      ]
    },
    {
      "given": "I. Nicholas",
      "family": "Crispe",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Section of Immunobiology, Yale School of Medicine, New Haven, CT 06520"
        }
      ]
    }
  ],
  "member": "286",
  "reference": [
    {
      "key": "2022123115060736200_R1",
      "doi-asserted-by": "crossref",
      "unstructured": "Huang, L., G. Soldevila, M. Leeker, R. A. Flavell, I. N. Crispe. 1994. The liver eliminates T cells undergoing antigen-triggered apoptosis in vivo. Immunity\u20081: 741",
      "DOI": "10.1016/S1074-7613(94)80016-2"
    },
    {
      "key": "2022123115060736200_R2",
      "doi-asserted-by": "crossref",
      "unstructured": "Wack, A., P. Dellaporta, I. N. Crispe, D. Kioussis. 1997. Multiple sites of post-activation CD8+ T cell disposal. Eur. J. Immunol.\u200827: 577",
      "DOI": "10.1002/eji.1830270302"
    },
    {
      "key": "2022123115060736200_R3",
      "doi-asserted-by": "crossref",
      "unstructured": "Russell, J. Q., G. J. Morrissette, M. Weidner, C. Vyas, D. Aleman-Hoey, R. C. Budd. 1998. Liver damage results preferentially from CD8+ T cells triggered by high affinity peptide antigens. J. Exp. Med.\u200888: 1147",
      "DOI": "10.1084/jem.188.6.1147"
    },
    {
      "key": "2022123115060736200_R4",
      "doi-asserted-by": "crossref",
      "unstructured": "Belz, G. T., J. D. Altman, P. C. Doherty. 1998. Characteristics of virus-specific CD8+ T cells in the liver during the control and resolution phases of influenza pneumonia. Proc. Natl. Acad. Sci USA\u200895: 13812",
      "DOI": "10.1073/pnas.95.23.13812"
    },
    {
      "key": "2022123115060736200_R5",
      "doi-asserted-by": "crossref",
      "unstructured": "Crispe, I. N., W. Z. Mehal. 1996. Strange brew, T cells in the liver. Immunol. Today\u200817: 522",
      "DOI": "10.1016/S0167-5699(96)80906-6"
    },
    {
      "key": "2022123115060736200_R6",
      "doi-asserted-by": "crossref",
      "unstructured": "Calne, R. Y., R. A. Sells, J. R. Pena, D. R. Davis, P. R. Millard, B. M. Herbertson, R. M. Binns, D. Davies. 1969. Induction of immunological tolerance by porcine liver allografts. Nature\u2008223: 472",
      "DOI": "10.1038/223472a0"
    },
    {
      "key": "2022123115060736200_R7",
      "doi-asserted-by": "crossref",
      "unstructured": "Cantor, H. M., A. E. Dumont. 1967. Hepatic suppression of sensitisation to antigen absorbed into the portal system. Nature\u2008215: 744",
      "DOI": "10.1038/215744a0"
    },
    {
      "key": "2022123115060736200_R8",
      "doi-asserted-by": "crossref",
      "unstructured": "Runyon, B. A., D. R. LaBrecque, S. Anuras. 1980. The spectrum of liver disease in systemic lupus erythematosus: report of 33 histologically-proved cases and review of the literature. Am. J. Med.\u200869: 187",
      "DOI": "10.1016/0002-9343(80)90378-2"
    },
    {
      "key": "2022123115060736200_R9",
      "unstructured": "Shiffman, M. L.. 1997. Immune disorders and the liver. N. Gitlin, ed. The Liver and Systemic Disease\u2008147-158. Churchill Livingstone, London."
    },
    {
      "key": "2022123115060736200_R10",
      "doi-asserted-by": "crossref",
      "unstructured": "Iwakoshi, N. N., I. Goldschneider, F. Tausche, J. P. Mordes, A. A. Rossini, D. L. Greiner. 1998. High frequency apoptosis of recent thymic emigrants in the liver of lymphopenic diabetes-prone BioBreeding rats. J. Immunol.\u2008160: 5838",
      "DOI": "10.4049/jimmunol.160.12.5838"
    },
    {
      "key": "2022123115060736200_R11",
      "doi-asserted-by": "crossref",
      "unstructured": "Huang, L., K. Sye, I. N. Crispe. 1994. Proliferation and apoptosis of B220+ CD4\u2212CD8\u2212TCR \u03b1\u03b2 intermediate T cells in the liver of normal adult mice: implication for lpr pathogenesis. Int. Immunol.\u20086: 533",
      "DOI": "10.1093/intimm/6.4.533"
    },
    {
      "key": "2022123115060736200_R12",
      "doi-asserted-by": "crossref",
      "unstructured": "Hashimoto, W., K. Takeda, R. Anzi, K. Ogasawara, H. Sakihari, K. Sugiura, S. Seki, K. Kumagai. 1995. Cytotoxic NK1.1 Ag+ \u03b1\u03b2 T cells with intermediate TCR induced in the liver of mice by IL-12. J. Immunol.\u2008154: 4333",
      "DOI": "10.4049/jimmunol.154.9.4333"
    },
    {
      "key": "2022123115060736200_R13",
      "doi-asserted-by": "crossref",
      "unstructured": "Watanabe, H., C. Miyaji, S. Seki, T. Abo. 1996. c-kit+ stem cells and thymocyte precursors in livers of adult mice. J. Exp. Med.\u2008184: 687",
      "DOI": "10.1084/jem.184.2.687"
    },
    {
      "key": "2022123115060736200_R14",
      "unstructured": "Crispe, I. N.. 1998. The liver: a unique immunologic environment. J. L. Boyer, ed. Progress in Liver Diseases\u2008109-124. W. B. Saunders, Philadelphia."
    },
    {
      "key": "2022123115060736200_R15",
      "unstructured": "Iiai, T., H. Watanabe, S. Seki, K. Sugiura, K. Hirokawa, M. Utsuyama, H. Takahashi-Iwanaga, T. Iwanaga, T. Ohteki, T. Abo. 1992. Ontogeny and development of extrathymic T cells in mouse liver. Immunology\u200877: 556"
    },
    {
      "key": "2022123115060736200_R16",
      "doi-asserted-by": "crossref",
      "unstructured": "Sato, K., K. Ohtsuka, K. Hasegawa, S. Yamagiwa, H. Watanabe, H. Asakura, S. Yamagiwa, H. Watanabe, H. Asakura, T. Abo. 1995. Evidence for extrathymic generation of intermediate T cell receptor cells in livers revealed in thymectomized, irradiated mice subjected to bone marrow transplantation. J. Exp. Med.\u2008182: 759",
      "DOI": "10.1084/jem.182.3.759"
    },
    {
      "key": "2022123115060736200_R17",
      "doi-asserted-by": "crossref",
      "unstructured": "Rubenstein, D., A. K. Roska, P. E. Lipsky. 1987. Antigen presentation by liver sinusoidal cells after antigen exposure in vivo. J. Immunol.\u2008138: 1377",
      "DOI": "10.4049/jimmunol.138.5.1377"
    },
    {
      "key": "2022123115060736200_R18",
      "doi-asserted-by": "crossref",
      "unstructured": "Magilavy, D. B., F. W. Fitchand, T. E. Gajewski. 1989. Murine hepatic accessory cells support the proliferation of Th1 but not Th2 helper T lymphocyte clones. J. Exp. Med.\u2008170: 985",
      "DOI": "10.1084/jem.170.3.985"
    },
    {
      "key": "2022123115060736200_R19",
      "doi-asserted-by": "crossref",
      "unstructured": "Lohse, A. W., P. A. Knolle, K. Bilo, A. Uhrig, C. Waldmann, M. Ibe, E. Schmitt, G. Gerken, K.-H. Meyer Zum Buschenfelde. 1996. Antigen presenting function and B7 expression of murine sinusoidal endothelial cells and Kupffer cells. Gastroenterology\u2008110: 1175",
      "DOI": "10.1053/gast.1996.v110.pm8613007"
    },
    {
      "key": "2022123115060736200_R20",
      "doi-asserted-by": "crossref",
      "unstructured": "Butcher, E. C., L. J. Picker. 1996. Lymphocyte homing and homeostasis. Science\u2008272: 60",
      "DOI": "10.1126/science.272.5258.60"
    },
    {
      "key": "2022123115060736200_R21",
      "doi-asserted-by": "crossref",
      "unstructured": "Salmi, M., S. Jalkanen. 1997. How do lymphocytes know where to go: current concepts and enigmas of lymphocyte homing. Adv. Immunol.\u200864: 139",
      "DOI": "10.1016/S0065-2776(08)60889-5"
    },
    {
      "key": "2022123115060736200_R22",
      "unstructured": "Jones, A. L.. 1996. Anatomy of the normal liver. D. Zakim, and T. D. Boyer, eds. Hepatology: A Textbook of Liver Diseases\u20081-27. W. B. Saunders, Philadelphia."
    },
    {
      "key": "2022123115060736200_R23",
      "doi-asserted-by": "crossref",
      "unstructured": "Scoazec, J. Y., G. Feldmann. 1994. The cell adhesion molecules of hepatic sinusoidal endothelial cells. J. Hepatol.\u200820: 296",
      "DOI": "10.1016/S0168-8278(05)80072-8"
    },
    {
      "key": "2022123115060736200_R24",
      "unstructured": "Scoazec, J.-Y.. 1996. Adhesion molecules in normal human liver. Hepato-gastroenterology\u200843: 1103"
    },
    {
      "key": "2022123115060736200_R25",
      "doi-asserted-by": "crossref",
      "unstructured": "Sligh, J. E., Jr, C. M. Ballantyne, S. S. Rich, H. K. Hawkins, C. W. Smith, A. Bradley, A. L. Beaudet. 1993. Inflammatory and immune responses are impaired in mice deficient in intercellular adhesion molecule 1. Proc. Natl. Acad. Sci. USA\u200890: 8529",
      "DOI": "10.1073/pnas.90.18.8529"
    },
    {
      "key": "2022123115060736200_R26",
      "doi-asserted-by": "crossref",
      "unstructured": "Salmi, M., S. Jalkanen. 1992. A 90-kilodalton endothelial cell molecule mediating lymphocyte binding in humans. Science\u2008257: 1407",
      "DOI": "10.1126/science.1529341"
    },
    {
      "key": "2022123115060736200_R27",
      "doi-asserted-by": "crossref",
      "unstructured": "Salmi, M., S. Tohka, E. Berg, E. C. Butcher, S. Jalkanen. 1997. Vascular adhesion protein-1 (VAP-1) mediates lymphocyte subtype-specific, selectin-independent recognition of vascular endothelium in human LNs. J. Exp. Med.\u2008186: 589",
      "DOI": "10.1084/jem.186.4.589"
    },
    {
      "key": "2022123115060736200_R28",
      "doi-asserted-by": "crossref",
      "unstructured": "MacPhee, P. J., E. E. Schmidt, A. C. Groom. 1995. Intermittence of blood flow in liver sinusoids, studied by high resolution in vivo microscopy. Am. J. Physiol.\u2008269: G692",
      "DOI": "10.1152/ajpgi.1995.269.5.G692"
    },
    {
      "key": "2022123115060736200_R29",
      "doi-asserted-by": "crossref",
      "unstructured": "Panes, J., M. A. Perry, D. C. Anderson, A. Manning, B. Leone, G. Cepinskas, C. L. Rosenbloom, M. Miyasaka, P. R. Kvietys, N. Granger. 1995. Regional differences in constitutive and induced ICAM-1 expression in vivo. Am. J. Physiol.\u2008269: H1955",
      "DOI": "10.1152/ajpheart.1995.269.6.H1955"
    },
    {
      "key": "2022123115060736200_R30",
      "doi-asserted-by": "crossref",
      "unstructured": "Kim, S. K., D. S. Reed, W. R. Heath, F. Carbone, L. Lefrancois. 1997. Activation and migration of CD8 T cells in the intestinal mucosa. J. Immunol.\u2008159: 4295",
      "DOI": "10.4049/jimmunol.159.9.4295"
    },
    {
      "key": "2022123115060736200_R31",
      "doi-asserted-by": "crossref",
      "unstructured": "Butz, E. A., M.J. Bevan. 1998. Massive expansion of antigen-specific CD8+ T cells during an acute virus infection. Immunity\u20088: 167",
      "DOI": "10.1016/S1074-7613(00)80469-0"
    },
    {
      "key": "2022123115060736200_R32",
      "doi-asserted-by": "crossref",
      "unstructured": "Webb, S., C. Morris, J. Sprent. 1990. Extrathymic tolerance of mature T cells: clonal elimination as a consequence of immunity. Cell\u200863: 1249",
      "DOI": "10.1016/0092-8674(90)90420-J"
    },
    {
      "key": "2022123115060736200_R33",
      "doi-asserted-by": "crossref",
      "unstructured": "Kawabe, Y., A. Ochi. 1991. Programmed cell death and extrathymic reduction of V\u03b28+ CD4+ T cells in mice tolerant to Staphylococcus aureus enterotoxin B. Nature\u2008349: 245",
      "DOI": "10.1038/349245a0"
    },
    {
      "key": "2022123115060736200_R34",
      "doi-asserted-by": "crossref",
      "unstructured": "Huang, L., K. Sye, I. N. Crispe. 1993. Proliferation and apoptosis of B220+ CD4\u2212 CD8\u2212 TCRab intermediate T cells in the liver of normal adult mice: implications for lpr pathogenesis. Int. Immunol.\u20086: 533",
      "DOI": "10.1093/intimm/6.4.533"
    },
    {
      "key": "2022123115060736200_R35",
      "doi-asserted-by": "crossref",
      "unstructured": "Martin, S. J., C. P. Reutelingsperger, A. J. McGahon, J. A. Rader, R. C. van Schie, D. M. LaFace, D. R. Green. 1995. Early redistribution of plasma membrane phosphatidylserine is a general feature of apoptosis regardless of the initiating stimulus: inhibition by overexpression of Bcl-2 and Abl. J. Exp. Med.\u2008182: 1545",
      "DOI": "10.1084/jem.182.5.1545"
    },
    {
      "key": "2022123115060736200_R36",
      "doi-asserted-by": "crossref",
      "unstructured": "Crispe, I. N., L. Huang. 1994. Neonatal, moribund and undead T cells: the role of the liver in T cell development. Semin. Immunol.\u20086: 39",
      "DOI": "10.1006/smim.1994.1006"
    },
    {
      "key": "2022123115060736200_R37",
      "doi-asserted-by": "crossref",
      "unstructured": "Wong, J., B. Johnston, S. S. Lee, D. C. Bullard, W. C. Smith, A. L. Beaudet, P. A. Kubes. 1997. Minimal role for selectins in the recruitment of leukocytes into the inflamed liver microvasculature. J. Clin. Invest.\u200899: 2782",
      "DOI": "10.1172/JCI119468"
    },
    {
      "key": "2022123115060736200_R38",
      "doi-asserted-by": "crossref",
      "unstructured": "Henninger, D. D., J. Panes, M. Eppihimer, J. Russell, M. Gerritsen, D. C. Anderson, D. N. Granger. 1997. Cytokine-induced VCAM-1 and ICAM-1 expression in different organs of the mouse. J. Immunol.\u2008158: 825",
      "DOI": "10.4049/jimmunol.158.4.1825"
    },
    {
      "key": "2022123115060736200_R39",
      "unstructured": "Komatsu, S., S. Flores, E. Gerritsen, D. C. Anderson, D. N. Granger. 1997. Differential up-regulation of circulating soluble and endothelial cell intracellular adhesion molecule-1 in mice. Am. J. Pathol.\u2008151: 205"
    },
    {
      "key": "2022123115060736200_R40",
      "doi-asserted-by": "crossref",
      "unstructured": "McNab, G., J. L. Reeves, M. Salmi, S. Hubscher, S. Jalkanen, D. H. Adams. 1996. Vascular adhesion protein 1 mediates binding of T cells to human hepatic endothelium. Gastroenterology\u2008110: 522",
      "DOI": "10.1053/gast.1996.v110.pm8566600"
    },
    {
      "key": "2022123115060736200_R41",
      "doi-asserted-by": "crossref",
      "unstructured": "Murali-Krishna, K., J. D. Altman, M. Suresh, D. J. Sourdive, A. J. Zajac, J. D. Miller, J. Slansky, R. Ahmed. 1998. Counting antigen-specific CD8 T cells: a reevaluation of bystander activation during viral infection. Immunity\u20088: 177",
      "DOI": "10.1016/S1074-7613(00)80470-7"
    },
    {
      "key": "2022123115060736200_R42",
      "doi-asserted-by": "crossref",
      "unstructured": "Pardi, R., J. R. Bender, C. Dettori, E. Giannazza, E. G. Engleman. 1989. Heterogeneous distribution and transmembrane signaling properties of lymphocyte function-associated antigen (LFA-1) in human lymphocyte subsets. J. Immunol.\u2008143: 3157",
      "DOI": "10.4049/jimmunol.143.10.3157"
    },
    {
      "key": "2022123115060736200_R43",
      "doi-asserted-by": "crossref",
      "unstructured": "Savill, J., N. Hogg, C. Haslett. 1992. Thrombospondin cooperates with CD36 and the vitronectin receptor in macrophage recognition of neutrophils undergoing apoptosis. J. Clin. Invest.\u200890: 1513",
      "DOI": "10.1172/JCI116019"
    },
    {
      "key": "2022123115060736200_R44",
      "doi-asserted-by": "crossref",
      "unstructured": "Platt, N., H. Suzuki, Y. Kurihara, T. Kodama, S. Gordon. 1996. Role of the class A macrophage scavenger receptor in the phagocytosis of apoptotic thymocytes in vitro. Proc. Natl. Acad. Sci. USA\u200893: 12456",
      "DOI": "10.1073/pnas.93.22.12456"
    },
    {
      "key": "2022123115060736200_R45",
      "doi-asserted-by": "crossref",
      "unstructured": "Pape, K. A., A. Khoruts, A. Mondino, M. K. Jenkins. 1997. Inflammatory cytokines enhance the in vivo clonal expansion and differentiation of antigen-activated CD4+ T cells. J. Immunol.\u2008159: 591",
      "DOI": "10.4049/jimmunol.159.2.591"
    },
    {
      "key": "2022123115060736200_R46",
      "doi-asserted-by": "crossref",
      "unstructured": "Qian, S., L. Lu, F. Fu, Y. Li, W. Li, T. E. Starzal, J. J. Fung, A. W. Thomson. 1997. Apoptosis within spontaneously accepted mouse liver allografts. J. Immunol.\u2008158: 4654",
      "DOI": "10.4049/jimmunol.158.10.4654"
    },
    {
      "key": "2022123115060736200_R47",
      "doi-asserted-by": "crossref",
      "unstructured": "White, K. L., H. L. Snyder, U. Krzych. 1996. MHC class I-dependent presentation of exoerythrocytic antigens to CD8+ T lymphocytes is required for protective immunity against Plasmodium\u2008berghei. J. Immunol.\u2008156: 3374",
      "DOI": "10.4049/jimmunol.156.9.3374"
    },
    {
      "key": "2022123115060736200_R48",
      "doi-asserted-by": "crossref",
      "unstructured": "Nelson, D. R., C. G. Marousis, G. L. Davis, C. M. Rice, J. Wong, M. Houghton, J. Y. Lau. 1997. The role of hepatitis C virus-specific cytotoxic T lymphocytes in chronic hepatitis C. J. Immunol.\u2008158: 1473",
      "DOI": "10.4049/jimmunol.158.3.1473"
    },
    {
      "key": "2022123115060736200_R49",
      "doi-asserted-by": "crossref",
      "unstructured": "Koziel, M. J.. 1997. The role of immune responses in the pathogenesis of hepatitis C virus infection. J. Viral Hepatitis\u20084: (Suppl. 2):31",
      "DOI": "10.1111/j.1365-2893.1997.tb00178.x"
    },
    {
      "key": "2022123115060736200_R50",
      "doi-asserted-by": "crossref",
      "unstructured": "Dao, T., W. Z. Mehal, I. N. Crispe. 1998. IL-18 augments perforin-dependent cytotoxicity of liver NK-T cells. J. Immunol.\u2008161: 2217",
      "DOI": "10.4049/jimmunol.161.5.2217"
    },
    {
      "key": "2022123115060736200_R51",
      "doi-asserted-by": "crossref",
      "unstructured": "Guidotti, L. G., R. Rochford, J. Chung, M. Shapiro, P. Purcell, F. V. Chisari. 1999. Viral clearance without destruction of infected cells during acute HBV infection. Science\u2008284: 825",
      "DOI": "10.1126/science.284.5415.825"
    },
    {
      "key": "2022123115060736200_R52",
      "doi-asserted-by": "crossref",
      "unstructured": "Matzinger, P.. 1994. Tolerance, danger, and the extended family. Annu. Rev. Immunol.\u200812: 991",
      "DOI": "10.1146/annurev.iy.12.040194.005015"
    }
  ],
  "container-title": "The Journal of Immunology",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://journals.aai.org/jimmunol/article-pdf/163/6/3202/1110629/im189903202p.pdf",
      "content-type": "application/pdf",
      "content-version": "vor",
      "intended-application": "syndication"
    },
    {
      "URL": "https://journals.aai.org/jimmunol/article-pdf/163/6/3202/1110629/im189903202p.pdf",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2025,
        1,
        2
      ]
    ],
    "date-time": "2025-01-02T18:06:41Z",
    "timestamp": 1735841201000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://journals.aai.org/jimmunol/article/163/6/3202/32488/Selective-Retention-of-Activated-CD8-T-Cells-by"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        1999,
        9,
        15
      ]
    ]
  },
  "references-count": 52,
  "journal-issue": {
    "issue": "6",
    "published-print": {
      "date-parts": [
        [
          1999,
          9,
          15
        ]
      ]
    }
  },
  "URL": "http://dx.doi.org/10.4049/jimmunol.163.6.3202",
  "relation": {},
  "ISSN": [
    "0022-1767",
    "1550-6606"
  ],
  "subject": [],
  "published": {
    "date-parts": [
      [
        1999,
        9,
        15
      ]
    ]
  }
}