{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:28:26Z","timestamp":1791221306039,"version":"4.1.0"},"reference-count":60,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5443","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[1999,11,12]]},"abstract":"<jats:p>An understanding of how T cell memory is maintained is crucial for the rational design of vaccines. Memory T cells were shown to persist indefinitely in major histocompatibility complex (MHC) class I\u2013deficient mice and retained the ability to make rapid cytokine responses upon reencounter with antigen. In addition, memory CD8 T cells, unlike na\u0131\u0308ve cells, divided without MHC\u2013T cell receptor interactions. This \u201chomeostatic\u201d proliferation is likely to be important in maintaining memory T cell numbers in the periphery. Thus, after na\u0131\u0308ve CD8 T cells differentiate into memory cells, they evolve an MHC class I\u2013independent \u201clife-style\u201d and do not require further stimulation with specific or cross-reactive antigen for their maintenance.<\/jats:p>","DOI":"10.1126\/science.286.5443.1377","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T09:45:50Z","timestamp":1027763150000},"page":"1377-1381","source":"Crossref","is-referenced-by-count":526,"title":["Persistence of Memory CD8 T Cells in MHC Class I-Deficient Mice"],"prefix":"10.1126","volume":"286","author":[{"given":"Kaja","family":"Murali-Krishna","sequence":"first","affiliation":[{"name":"Emory Vaccine Center and Department of Microbiology and Immunology, Emory University, Atlanta, GA 30322, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa L.","family":"Lau","sequence":"additional","affiliation":[{"name":"Emory Vaccine Center and Department of Microbiology and Immunology, Emory University, Atlanta, GA 30322, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suryaprakash","family":"Sambhara","sequence":"additional","affiliation":[{"name":"Pasteur Merieux Connaught Canada, North York, Ontario M2R 3TA, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francois","family":"Lemonnier","sequence":"additional","affiliation":[{"name":"Departement du SIDA et des Retrovirus, Institut Pasteur, Paris 75724, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Altman","sequence":"additional","affiliation":[{"name":"Emory Vaccine Center and Department of Microbiology and Immunology, Emory University, Atlanta, GA 30322, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafi","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Emory Vaccine Center and Department of Microbiology and Immunology, Emory University, Atlanta, GA 30322, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/0167-5699(90)90083-L","volume":"11","author":"Beveley P. C. L.","year":"1990","unstructured":"Beveley P. C. L., Immunol. Today 11, 203 (1990);","journal-title":"Immunol. Today"},{"key":"e_1_3_1_2_3","doi-asserted-by":"publisher","DOI":"10.1016\/1074-7613(95)90077-2"},{"key":"e_1_3_1_2_4","first-page":"55","volume":"272","author":"Ahmed R.","year":"1996","unstructured":"Ahmed R., Gray D., Science 272, 55 (1996);","journal-title":"Science"},{"key":"e_1_3_1_2_5","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/S0952-7915(97)80084-2","volume":"9","author":"Sprent J.","year":"1997","unstructured":"Sprent J., Curr. Opin. Immunol. 9, 37 (1997);","journal-title":"Curr. Opin. Immunol."},{"key":"e_1_3_1_2_6","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/S0167-5699(97)80017-5","volume":"18","author":"Zinkernagel R. M.","year":"1997","unstructured":"Zinkernagel R. M., Hengartner H., Immunol. Today 18, 258 (1997);","journal-title":"Immunol. Today"},{"key":"e_1_3_1_2_7","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.16.1.201"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80470-7"},{"key":"e_1_3_1_4_2","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1038\/369652a0","volume":"369","author":"Hou S.","year":"1994","unstructured":"Hou S., et al., Nature 369, 652 (1994);","journal-title":"Nature"},{"key":"e_1_3_1_4_3","doi-asserted-by":"publisher","DOI":"10.1038\/369648a0"},{"key":"e_1_3_1_4_4","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1084\/jem.179.1.317","volume":"179","author":"Mullbacher A.","year":"1994","unstructured":"Mullbacher A., J. Exp. Med. 179, 317 (1994).","journal-title":"J. Exp. Med."},{"key":"e_1_3_1_5_2","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1126\/science.7535476","volume":"268","author":"McHeyzer-Williams M. G.","year":"1995","unstructured":"McHeyzer-Williams M. G., Davis M. M., Science 268, 106 (1995);","journal-title":"Science"},{"key":"e_1_3_1_5_3","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1084\/jem.186.9.1407","volume":"186","author":"Hamann D.","year":"1997","unstructured":"Hamann D., et al., J. Exp. Med. 186, 1407 (1997);","journal-title":"J. Exp. Med."},{"key":"e_1_3_1_5_4","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1084\/jem.186.6.859","volume":"186","author":"Lalvani A.","year":"1997","unstructured":"Lalvani A., et al., J. Exp. Med. 186, 859 (1997);","journal-title":"J. Exp. Med."},{"key":"e_1_3_1_5_5","doi-asserted-by":"crossref","first-page":"674","DOI":"10.4049\/jimmunol.161.2.674","volume":"161","author":"Kedl R. M.","year":"1998","unstructured":"Kedl R. M., Mescher M. F., J. Immunol. 161, 674 (1998);","journal-title":"J. Immunol."},{"key":"e_1_3_1_5_6","doi-asserted-by":"crossref","first-page":"2141","DOI":"10.1084\/jem.184.6.2141","volume":"184","author":"Pihlgren M.","year":"1998","unstructured":"Pihlgren M., et al., J. Exp. Med. 184, 2141 (1998);","journal-title":"J. Exp. Med."},{"key":"e_1_3_1_5_7","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1002\/(SICI)1521-4141(199901)29:01<291::AID-IMMU291>3.0.CO;2-K","volume":"29","author":"Bachmann M. F.","year":"1999","unstructured":"Bachmann M. F., et al., Eur. J. Immunol. 29, 291 (1999);","journal-title":"Eur. J. Immunol."},{"key":"e_1_3_1_5_8","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.6.2976"},{"key":"e_1_3_1_5_9","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1002\/(SICI)1521-4141(199901)29:01<284::AID-IMMU284>3.0.CO;2-C","volume":"29","author":"Zimmermann C.","year":"1999","unstructured":"Zimmermann C., et al., Eur. J. Immunol. 29, 284 (1999).","journal-title":"Eur. J. Immunol."},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80317-9"},{"key":"e_1_3_1_6_3","doi-asserted-by":"publisher","DOI":"10.1084\/jem.186.8.1223"},{"key":"e_1_3_1_6_4","doi-asserted-by":"publisher","DOI":"10.1084\/jem.186.8.1269"},{"key":"e_1_3_1_6_5","doi-asserted-by":"crossref","first-page":"3992","DOI":"10.4049\/jimmunol.161.8.3992","volume":"161","author":"Barthlott T.","year":"1998","unstructured":"Barthlott T., Wright R. J., Stockinger B., J. Immunol. 161, 3992 (1998);","journal-title":"J. Immunol."},{"key":"e_1_3_1_6_6","doi-asserted-by":"crossref","first-page":"3705","DOI":"10.4049\/jimmunol.160.8.3705","volume":"160","author":"Nesic D.","year":"1998","unstructured":"Nesic D., Vukmanovic S., J. Immunol. 160, 3705 (1998);","journal-title":"J. Immunol."},{"key":"e_1_3_1_6_7","doi-asserted-by":"crossref","first-page":"3795","DOI":"10.4049\/jimmunol.162.7.3795","volume":"162","author":"Boursalian T. E.","year":"1999","unstructured":"Boursalian T. E., Bottomly K., J. Immunol. 162, 3795 (1999);","journal-title":"J. Immunol."},{"key":"e_1_3_1_6_8","doi-asserted-by":"publisher","DOI":"10.1126\/science.284.5417.1187"},{"key":"e_1_3_1_6_9","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1016\/S1074-7613(00)80055-2","volume":"10","author":"Viret C.","year":"1999","unstructured":"Viret C., Wong F. S., Janeway C. A., Immunity 10, 559 (1999);","journal-title":"Immunity"},{"key":"e_1_3_1_6_10","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80092-8"},{"key":"e_1_3_1_6_11","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/S1074-7613(00)80093-X","volume":"11","author":"Goldrath A. W.","year":"1999","unstructured":"Goldrath A. W., Bevan M. J., Immunity 11, 183 (1999);","journal-title":"Immunity"},{"key":"e_1_3_1_6_12","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1084\/jem.190.3.367","volume":"190","author":"Bender J.","year":"1999","unstructured":"Bender J., et al., J. Exp. Med. 190, 367 (1999).","journal-title":"J. Exp. Med."},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.276.5321.2057"},{"key":"e_1_3_1_7_3","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.6.3065"},{"key":"e_1_3_1_8_2","unstructured":"FACS-purified CD8 T cells obtained from LCMV immune mice (>3 months after infection) were shown to be virus-free by plaque assay [<1 plaque-forming unit (PFU) per 5 \u00d7 10 6 cells] immunohistochemistry and a quantitative polymerase chain reaction assay (<1 genome equivalent per 10 5 CD8 T cells). Also the sorted CD8 T cells were unable to stimulate LCMV-specific CTL clones in vitro or prime host T cells in vivo after adoptive transfer into na\u0131\u0308ve mice."},{"key":"e_1_3_1_9_2","unstructured":"K. Murali-Krishna et al. data not shown."},{"key":"e_1_3_1_10_2","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1084\/jem.183.4.1367","volume":"183","author":"Zimmerman C.","year":"1996","unstructured":"Zimmerman C., et al., J. Exp. Med. 183, 1367 (1996);","journal-title":"J. Exp. Med."},{"key":"e_1_3_1_10_3","doi-asserted-by":"publisher","DOI":"10.1126\/science.272.5270.1947"},{"key":"e_1_3_1_10_4","doi-asserted-by":"crossref","first-page":"3179","DOI":"10.1002\/eji.1830261251","volume":"26","author":"Bruno L.","year":"1996","unstructured":"Bruno L., von Boehmer H., Kirberg J., Eur. J. Immunol. 26, 3179 (1996).","journal-title":"Eur. J. Immunol."},{"key":"e_1_3_1_11_2","unstructured":"D b\u2212\/\u2212 and K b\u2212\/\u2212 mice ["},{"key":"e_1_3_1_11_3","doi-asserted-by":"crossref","first-page":"2043","DOI":"10.1084\/jem.185.12.2043","volume":"185","author":"Pascolo S.","year":"1997","unstructured":"Pascolo S., et al., J. Exp. Med. 185, 2043 (1997);","journal-title":"J. Exp. Med."},{"key":"e_1_3_1_11_4","unstructured":"] were back-crossed to each other and then to \u03b2 2 M \u2212\/\u2212 mice to obtain D b\u2212\/\u2212 \u00d7 K b\u2212\/\u2212 \u00d7 \u03b2 2 M \u2212\/\u2212 mice. All of the mice were on a C57BL\/6 background."},{"key":"e_1_3_1_12_2","doi-asserted-by":"crossref","first-page":"12492","DOI":"10.1073\/pnas.95.21.12492","volume":"95","author":"Vugmeyster Y.","year":"1998","unstructured":"Vugmeyster Y., et al., Proc. Natl. Acad. Sci. U.S.A. 95, 12492 (1998).","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"e_1_3_1_13_2","unstructured":"This hyperproliferation of endogenous CD8 T cells of D b\u2212\/\u2212 \u00d7 K b\u2212\/\u2212 \u00d7 \u03b2 2 M \u2212\/\u2212 mice is unlikely to be due to stimulation with MHC class I present on the transferred CD8 T cells because even in \u2212\/\u2212 mice that have not received any cell transfer the endogenous CD8 T cells exhibit a similar pattern of hyperproliferation (8)."},{"key":"e_1_3_1_14_2","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1038\/346629a0","volume":"346","author":"Pircher H.","year":"1990","unstructured":"Pircher H., et al., Nature 346, 629 (1990).","journal-title":"Nature"},{"key":"e_1_3_1_15_2","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1093\/intimm\/3.11.1077","volume":"3","author":"Pereira P.","year":"1991","unstructured":"Pereira P., Rocha B., Int. Immunol. 3, 1077 (1991);","journal-title":"Int. Immunol."},{"key":"e_1_3_1_15_3","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1084\/jem.174.3.717","volume":"174","author":"Sprent J.","year":"1991","unstructured":"Sprent J., et al., J. Exp. Med. 174, 717 (1991);","journal-title":"J. Exp. Med."},{"key":"e_1_3_1_15_4","first-page":"514","volume":"84","author":"McDonagh M.","year":"1995","unstructured":"McDonagh M., Bell E. B., Immunology 84, 514 (1995);","journal-title":"Immunology"},{"key":"e_1_3_1_15_5","doi-asserted-by":"crossref","first-page":"3179","DOI":"10.1002\/eji.1830261251","volume":"26","author":"Bruno L.","year":"1996","unstructured":"Bruno L., von Boehmer H., Kirberg J., Eur. J. Immunol. 26, 3179 (1996).","journal-title":"Eur. J. Immunol."},{"key":"e_1_3_1_16_2","unstructured":"Although Tanchot et al. (6) reached a different conclusion there are many similarities between their study and ours. In agreement with us Tanchot et al. (6) found that na\u0131\u0308ve CD8 T cells were more dependent on MHC class I molecules than memory T cells. For example they showed that HY-specific memory CD8 T cells (which recognize HY peptide presented by D b ) were able to expand in D b\u2212\/\u2212 mice whereas na\u0131\u0308ve CD8 T cells disappeared. Similar to our finding they also reported proliferation of HY-specific memory CD8 T cells in MHC class I \u2212\/\u2212 (D b\u2212\/\u2212 \u00d7 \u03b2 2 M \u2212\/\u2212 ) mice. However in contrast to our results they found that despite this proliferation HY-specific memory CD8 T cells declined (>20-fold drop in 2 weeks) in MHC class I \u2212\/\u2212 mice. A potential complication of the Tanchot et al. (6) study was that they transferred HY-specific memory CD8 T cells from B6 mice into D b\u2212\/\u2212 \u00d7 \u03b2 2 M \u2212\/\u2212 mice that were on a 129 \u00d7 B6 background. It is well established that mice with 129 background can pose problems in adoptive transfer experiments and in fact when we used the same mice that Rocha used in her study neither CD8 nor CD4 T cells from B6 mice survived after adoptive transfer (20). However new preliminary experiments with MHC class I \u2212\/\u2212 mice backcrossed to B6 show the same results with HY transgenic memory T cells (B. Rocha personal communication). Thus it is possible that differences between our findings may reflect a unique property of the HY-specific transgenic CD8 T cells. Consistent with this is the observation that unlike most na\u0131\u0308ve CD8 T cells (either transgenic or polyclonal) na\u0131\u0308ve HY transgenic T cells do not divide even in +\/+ lymphopenic mice. The study by Markiewicz et al. (6) is difficult to compare with ours because they examined the survival of in vitro\u2013activated HY-specific effector and na\u0131\u0308ve CD8 T cells after transfer into TAP \u2212\/\u2212 mice. They found that the activated cell population was more dependent on MHC class I for their survival than na\u0131\u0308ve CD8 T cells. Thus it is conceivable that survival of CD8 effectors (which are highly susceptible to apoptosis) and not memory CD8 T cells was being analyzed in their study."},{"key":"e_1_3_1_17_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.286.5443.1381"},{"key":"e_1_3_1_18_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.280.5365.905"},{"key":"e_1_3_1_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80373-6"},{"key":"e_1_3_1_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80642-1"},{"key":"e_1_3_1_20_3","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/S1074-7613(00)80605-6","volume":"9","author":"Bird J. J.","year":"1998","unstructured":"Bird J. J., et al., Immunity 9, 229 (1998);","journal-title":"Immunity"},{"key":"e_1_3_1_20_4","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1084\/jem.188.1.103","volume":"188","author":"Fitzpatrick D. R.","year":"1998","unstructured":"Fitzpatrick D. R., et al., J. Exp. Med. 188, 103 (1998);","journal-title":"J. Exp. Med."},{"key":"e_1_3_1_20_5","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1016\/S1074-7613(00)80644-5","volume":"6","author":"Moran M.","year":"1998","unstructured":"Moran M., Miceli M. C., Immunity 6, 787 (1998);","journal-title":"Immunity"},{"key":"e_1_3_1_20_6","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.1084\/jem.189.10.1521","volume":"189","author":"Bachmann M. F.","year":"1999","unstructured":"Bachmann M. F., et al., J. Exp. Med. 189, 1521 (1999).","journal-title":"J. Exp. Med."},{"key":"e_1_3_1_21_2","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/ng0597-19","volume":"16","author":"Simpsons E. M.","year":"1997","unstructured":"Simpsons E. M., et al., Nature Genet. 16, 19 (1997).","journal-title":"Nature Genet."},{"key":"e_1_3_1_22_2","unstructured":"Thy1.1 + C57BL\/6 mice were immunized with 2 \u00d7 10 5 PFU of LCMV Armstrong and rested for 3 to 8 months. Spleen cells from groups of these mice were pooled stained for surface CD8 sorted in a FACS-Vantage (Becton Dickinson) and transferred intravenously into irradiated (550R) Thy1.2 recipients. Before transfer LCMV-specific memory CD8 T cell numbers were determined by staining with MHC class I tetramers and by single-cell assays (ELISPOT and intracellular stain) measuring IFN-\u03b3 production (2). After adoptive transfer the donor CD8 T cells were identified by the Thy1.1 marker and LCMV-specific memory cells were quantitated with MHC class I tetramers and by cytokine assays (2). Memory cells transferred into MHC class I\u2013deficient mice were analyzed for cytokine production by adding spleen cells from uninfected +\/+ mice (1:1 ratio) to present the peptide. LCMV-specific memory CD8 T cells were distinguished from effector cells on the basis of minimal to no ex vivo cytolytic activity (>20-fold lower than effector cells on a per cell basis) low levels of CD69 low IL-2R\u03b1 (CD25) and low transferrin receptor (CD71) expression. They also differed from na\u0131\u0308ve cells on the basis of high expression of cell surface markers CD44 and Ly6C and their ability to induce rapid cytokine responses."},{"key":"e_1_3_1_23_2","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1038\/359330a0","volume":"359","author":"Bix M.","year":"1992","unstructured":"Bix M., Raulet D., Nature 359, 330 (1992).","journal-title":"Nature"},{"key":"e_1_3_1_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-1759(94)90236-4"},{"key":"e_1_3_1_25_2","unstructured":"Supported by NIH grants AI30048 and NS21496."}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.286.5443.1377","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,13]],"date-time":"2024-01-13T10:31:17Z","timestamp":1705141877000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.286.5443.1377"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1999,11,12]]},"references-count":60,"journal-issue":{"issue":"5443","published-print":{"date-parts":[[1999,11,12]]}},"alternative-id":["10.1126\/science.286.5443.1377"],"URL":"https:\/\/doi.org\/10.1126\/science.286.5443.1377","relation":{},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[1999,11,12]]}}}