Publications

2024

Ali Maisam Afzali, Lucy Nirschl, Christopher Sie, Monika Pfaller, Oleksii Ulianov, Tobias Hassler, Christine Federle, Elisabetta Petrozziello, Sudhakar Reddy Kalluri, Hsin Hsiang Chen, Sofia Tyystjärvi, Andreas Muschaweckh, Katja Lammens, Claire Delbridge, Andreas Büttner, Katja Steiger, Gönül Seyhan, Ole Petter Ottersen, Rupert Öllinger, Roland Rad, Sebastian Jarosch, Adrian Straub, Anton Mühlbauer, Simon Grassmann, Bernhard Hemmer, Jan P. Böttcher, Ingrid Wagner, Mario Kreutzfeldt, Doron Merkler, Irene Bonafonte Pardàs, Marc Schmidt Supprian, Veit R. Buchholz, Sylvia Heink, Dirk H. Busch, Ludger Klein & Thomas Korn (2024 Feb 21) B cells orchestrate tolerance to the neuromyelitis optica autoantigen AQP4. Nature. https://doi.org/10.1038/s41586-024-07079-8

2020

Voboril, M., Brabec, T., Dobes, J., Splichalova, I., Brezina, J., Cepkova, A., Dobesova, M., Aidarova, A., Kubovciak, J., Tsyklauri, O., Stepanek, O., Benes, V., Sedlacek, R., Klein, L., Kolar, M., and Filipp, D. (2020). Toll-like receptor signaling in thymic epithelium controls monocyte-derived dendritic cell recruitment and Treg generation. Nat Commun 11:2361.
PMID: 32398640, https://www.ncbi.nlm.nih.gov/pubmed/32398640

Schober, K., Voit, F., Grassmann, S., Muller, T.R., Eggert, J., Jarosch, S., Weissbrich, B., Hoffmann, P., Borkner, L., Nio, E., Fanchi, L., Clouser, C.R., Radhakrishnan, A., Mihatsch, L., Luckemeier, P., Leube, J., Dossinger, G., Klein, L., Neuenhahn, M., Oduro, J.D., Cicin-Sain, L., Buchholz, V.R., and Busch, D.H. (2020). Reverse TCR repertoire evolution toward dominant low-affinity clones during chronic CMV infection. Nat Immunol 21:434-441.
PMID: 32205883, https://www.ncbi.nlm.nih.gov/pubmed/32205883

2019

Yamano, T., Steinert, M., Steer, B., Klein, L., Hammerschmidt, W., and Adler, H. (2019a). B cells latently infected with murine gammaherpesvirus 68 (MHV-68) are present in the mouse thymus-A step toward immune evasion? Eur J Immunol 49:351-352.
PMID: 30488950, https://www.ncbi.nlm.nih.gov/pubmed/30488950

Yamano, T., Dobes, J., Voboril, M., Steinert, M., Brabec, T., Zietara, N., Dobesova, M., Ohnmacht, C., Laan, M., Peterson, P., Benes, V., Sedlacek, R., Hanayama, R., Kolar, M., Klein, L., and Filipp, D. (2019b). Aire-expressing ILC3-like cells in the lymph node display potent APC features. J Exp Med 216:1027-1037.
PMID: 30918005, https://www.ncbi.nlm.nih.gov/pubmed/30918005

Klein, L., Robey, E.A., and Hsieh, C.S. (2019). Central CD4(+) T cell tolerance: deletion versus regulatory T cell differentiation. Nat Rev Immunol 19:7-18.
PMID: 30420705, https://www.ncbi.nlm.nih.gov/pubmed/30420705

Hassler, T., Urmann, E., Teschner, S., Federle, C., Dileepan, T., Schober, K., Jenkins, M.K., Busch, D.H., Hinterberger, M., and Klein, L. (2019). Inventories of naive and tolerant mouse CD4 T cell repertoires reveal a hierarchy of deleted and diverted T cell receptors. Proc Natl Acad Sci U S A 116:18537-18543.
PMID: 31451631, https://www.ncbi.nlm.nih.gov/pubmed/31451631

2018

Dobes, J., Edenhofer, F., Voboril, M., Brabec, T., Dobesova, M., Cepkova, A., Klein, L., Rajewsky, K., and Filipp, D. (2018). A novel conditional Aire allele enables cell-specific ablation of the immune tolerance regulator Aire. Eur J Immunol 48:546-548.
PMID: 29193031, https://www.ncbi.nlm.nih.gov/pubmed/29193031

2017

Wang, L., Winnewisser, J., Federle, C., Jessberger, G., Nave, K.A., Werner, H.B., Kyewski, B., Klein, L., and Hinterberger, M. (2017). Epitope-Specific Tolerance Modes Differentially Specify Susceptibility to Proteolipid Protein-Induced Experimental Autoimmune Encephalomyelitis. Front Immunol 8:1511.
PMID: 29170668, https://www.ncbi.nlm.nih.gov/pubmed/29170668

2016

von Rohrscheidt, J., Petrozziello, E., Nedjic, J., Federle, C., Krzyzak, L., Ploegh, H.L., Ishido, S., Steinkasserer, A., and Klein, L. (2016). Thymic CD4 T cell selection requires attenuation of March8-mediated MHCII turnover in cortical epithelial cells through CD83. J Exp Med 213:1685-1694.
PMID: 27503071, https://www.ncbi.nlm.nih.gov/pubmed/27503071

Pasquarella, A., Ebert, A., Pereira de Almeida, G., Hinterberger, M., Kazerani, M., Nuber, A., Ellwart, J., Klein, L., Busslinger, M., and Schotta, G. (2016). Retrotransposon derepression leads to activation of the unfolded protein response and apoptosis in pro-B cells. Development 143:1788-1799.
PMID: 27013243, https://www.ncbi.nlm.nih.gov/pubmed/27013243

2015

Yamano, T., Steinert, M., and Klein, L. (2015a). Thymic B Cells and Central T Cell Tolerance. Front Immunol 6:376.
PMID: 26257742, https://www.ncbi.nlm.nih.gov/pubmed/26257742

Yamano, T., Nedjic, J., Hinterberger, M., Steinert, M., Koser, S., Pinto, S., Gerdes, N., Lutgens, E., Ishimaru, N., Busslinger, M., Brors, B., Kyewski, B., and Klein, L. (2015b). Thymic B Cells Are Licensed to Present Self Antigens for Central T Cell Tolerance Induction. Immunity 42:1048-1061.
PMID: 26070482, https://www.ncbi.nlm.nih.gov/pubmed/26070482

Warth, S.C., Hoefig, K.P., Hiekel, A., Schallenberg, S., Jovanovic, K., Klein, L., Kretschmer, K., Ansel, K.M., and Heissmeyer, V. (2015). Induced miR-99a expression represses Mtor cooperatively with miR-150 to promote regulatory T-cell differentiation. EMBO J 34:1195-1213.
PMID: 25712478, https://www.ncbi.nlm.nih.gov/pubmed/25712478

Klein, L. (2015). Aire Gets Company for Immune Tolerance. Cell 163:794-795.
PMID: 26544932, https://www.ncbi.nlm.nih.gov/pubmed/26544932

2014

Vahl, J.C., Drees, C., Heger, K., Heink, S., Fischer, J.C., Nedjic, J., Ohkura, N., Morikawa, H., Poeck, H., Schallenberg, S., Riess, D., Hein, M.Y., Buch, T., Polic, B., Schonle, A., Zeiser, R., Schmitt-Graff, A., Kretschmer, K., Klein, L., Korn, T., Sakaguchi, S., and Schmidt-Supprian, M. (2014). Continuous T cell receptor signals maintain a functional regulatory T cell pool. Immunity 41:722-736.
PMID: 25464853, https://www.ncbi.nlm.nih.gov/pubmed/25464853

Klein, L., Kyewski, B., Allen, P.M., and Hogquist, K.A. (2014). Positive and negative selection of the T cell repertoire: what thymocytes see (and don't see). Nat Rev Immunol 14:377-391.
PMID: 24830344, https://www.ncbi.nlm.nih.gov/pubmed/24830344

2013

Wu, C., Aichinger, M., Nedjic, J., and Klein, L. (2013). Thymic epithelial cells use macroautophagy to turn their inside out for CD4 T cell tolerance. Autophagy 9:931-932.
PMID: 23548947, https://www.ncbi.nlm.nih.gov/pubmed/23548947

Aichinger, M., Wu, C., Nedjic, J., and Klein, L. (2013). Macroautophagy substrates are loaded onto MHC class II of medullary thymic epithelial cells for central tolerance. J Exp Med 210:287-300.
PMID: 23382543, https://www.ncbi.nlm.nih.gov/pubmed/23382543

2012

Klein, L., and Jovanovic, K. (2012). Regulatory T cell differentiation: turning harmful into useful. Immunity 37:441-443.
PMID: 22999949, https://www.ncbi.nlm.nih.gov/pubmed/22999949

Aichinger, M., Hinterberger, M., and Klein, L. (2012). Probing gene function in thymic epithelial cells. Eur J Cell Biol 91:24-30.
PMID: 21392839, https://www.ncbi.nlm.nih.gov/pubmed/21392839

2011

Wirnsberger, G., Hinterberger, M., and Klein, L. (2011). Regulatory T-cell differentiation versus clonal deletion of autoreactive thymocytes. Immunol Cell Biol 89:45-53.
PMID: 21042335, https://www.ncbi.nlm.nih.gov/pubmed/21042335

Klein, L., and Jovanovic, K. (2011). Regulatory T cell lineage commitment in the thymus. Semin Immunol 23:401-409.
PMID: 21733719, https://www.ncbi.nlm.nih.gov/pubmed/21733719

Klein, L., Hinterberger, M., von Rohrscheidt, J., and Aichinger, M. (2011). Autonomous versus dendritic cell-dependent contributions of medullary thymic epithelial cells to central tolerance. Trends Immunol 32:188-193.
PMID: 21493141, https://www.ncbi.nlm.nih.gov/pubmed/21493141

Hinterberger, M., Wirnsberger, G., and Klein, L. (2011). B7/CD28 in central tolerance: costimulation promotes maturation of regulatory T cell precursors and prevents their clonal deletion. Front Immunol 2:30.
PMID: 22566820, https://www.ncbi.nlm.nih.gov/pubmed/22566820

Bertossi, A., Aichinger, M., Sansonetti, P., Lech, M., Neff, F., Pal, M., Wunderlich, F.T., Anders, H.J., Klein, L., and Schmidt-Supprian, M. (2011). Loss of Roquin induces early death and immune deregulation but not autoimmunity. J Exp Med 208:1749-1756.
PMID: 21844204, https://www.ncbi.nlm.nih.gov/pubmed/21844204

2010

Klein, L., Munz, C., and Lunemann, J.D. (2010). Autophagy-mediated antigen processing in CD4(+) T cell tolerance and immunity. FEBS Lett 584:1405-1410.
PMID: 20074571, https://www.ncbi.nlm.nih.gov/pubmed/20074571

Hinterberger, M., Aichinger, M., Prazeres da Costa, O., Voehringer, D., Hoffmann, R., and Klein, L. (2010). Autonomous role of medullary thymic epithelial cells in central CD4(+) T cell tolerance. Nat Immunol 11:512-519.
PMID: 20431619, https://www.ncbi.nlm.nih.gov/pubmed/20431619

2009

Wirnsberger, G., Mair, F., and Klein, L. (2009). Regulatory T cell differentiation of thymocytes does not require a dedicated antigen-presenting cell but is under T cell-intrinsic developmental control. Proc Natl Acad Sci U S A 106:10278-10283.
PMID: 19515822, https://www.ncbi.nlm.nih.gov/pubmed/19515822

Nedjic, J., Aichinger, M., Mizushima, N., and Klein, L. (2009). Macroautophagy, endogenous MHC II loading and T cell selection: the benefits of breaking the rules. Curr Opin Immunol 21:92-97.
PMID: 19246181, https://www.ncbi.nlm.nih.gov/pubmed/19246181

Klein, L., Hinterberger, M., Wirnsberger, G., and Kyewski, B. (2009). Antigen presentation in the thymus for positive selection and central tolerance induction. Nat Rev Immunol 9:833-844.
PMID: 19935803, https://www.ncbi.nlm.nih.gov/pubmed/19935803

Klein, L. (2009). Dead man walking: how thymocytes scan the medulla. Nat Immunol 10:809-811.
PMID: 19621041, https://www.ncbi.nlm.nih.gov/pubmed/19621041

2008

Nedjic, J., Aichinger, M., and Klein, L. (2008a). Autophagy and T cell education in the thymus: eat yourself to know yourself. Cell Cycle 7:3625-3628.
PMID: 19029805, https://www.ncbi.nlm.nih.gov/pubmed/19029805

Nedjic, J., Aichinger, M., and Klein, L. (2008b). A novel role for autophagy in T cell education. Autophagy 4:1090-1092.
PMID: 18927488, https://www.ncbi.nlm.nih.gov/pubmed/18927488

Nedjic, J., Aichinger, M., Emmerich, J., Mizushima, N., and Klein, L. (2008c). Autophagy in thymic epithelium shapes the T-cell repertoire and is essential for tolerance. Nature 455:396-400.
PMID: 18701890, https://www.ncbi.nlm.nih.gov/pubmed/18701890

2007

Aschenbrenner, K., D'Cruz, L.M., Vollmann, E.H., Hinterberger, M., Emmerich, J., Swee, L.K., Rolink, A., and Klein, L. (2007). Selection of Foxp3+ regulatory T cells specific for self antigen expressed and presented by Aire+ medullary thymic epithelial cells. Nat Immunol 8:351-358.
PMID: 17322887, https://www.ncbi.nlm.nih.gov/pubmed/17322887

2006

Kyewski, B., and Klein, L. (2006). A central role for central tolerance. Annu Rev Immunol 24:571-606.
PMID: 16551260, https://www.ncbi.nlm.nih.gov/pubmed/16551260

2005

Klein, L., Emmerich, J., d'Cruz, L., Aschenbrenner, K., and Khazaie, K. (2005). Selection and behavior of CD4+ CD25+ T cells in vivo: lessons from T cell receptor transgenic models. Curr Top Microbiol Immunol 293:73-87.
PMID: 15981476, https://www.ncbi.nlm.nih.gov/pubmed/15981476

D'Cruz, L.M., and Klein, L. (2005). Development and function of agonist-induced CD25+Foxp3+ regulatory T cells in the absence of interleukin 2 signaling. Nat Immunol 6:1152-1159.
PMID: 16227983, https://www.ncbi.nlm.nih.gov/pubmed/16227983

Bos, R., van Duikeren, S., van Hall, T., Kaaijk, P., Taubert, R., Kyewski, B., Klein, L., Melief, C.J., and Offringa, R. (2005). Expression of a natural tumor antigen by thymic epithelial cells impairs the tumor-protective CD4+ T-cell repertoire. Cancer Res 65:6443-6449.
PMID: 16024649, https://www.ncbi.nlm.nih.gov/pubmed/16024649

2004

Havari, E., Lennon-Dumenil, A.M., Klein, L., Neely, D., Taylor, J.A., McInerney, M.F., Wucherpfennig, K.W., and Lipes, M.A. (2004). Expression of the B7.1 costimulatory molecule on pancreatic beta cells abrogates the requirement for CD4 T cells in the development of type 1 diabetes. J Immunol 173:787-796.
PMID: 15240665, https://www.ncbi.nlm.nih.gov/pubmed/15240665

2003

von Boehmer, H., Aifantis, I., Gounari, F., Azogui, O., Haughn, L., Apostolou, I., Jaeckel, E., Grassi, F., and Klein, L. (2003). Thymic selection revisited: how essential is it? Immunol Rev 191:62-78.
PMID: 12614352, https://www.ncbi.nlm.nih.gov/pubmed/12614352

Klein, L., Trautman, L., Psarras, S., Schnell, S., Siermann, A., Liblau, R., von Boehmer, H., and Khazaie, K. (2003a). Visualizing the course of antigen-specific CD8 and CD4 T cell responses to a growing tumor. Eur J Immunol 33:806-814.
PMID: 12616501, https://www.ncbi.nlm.nih.gov/pubmed/12616501

Klein, L., Khazaie, K., and von Boehmer, H. (2003b). In vivo dynamics of antigen-specific regulatory T cells not predicted from behavior in vitro. Proc Natl Acad Sci U S A 100:8886-8891.
PMID: 12857946, https://www.ncbi.nlm.nih.gov/pubmed/12857946

Jaeckel, E., Klein, L., Martin-Orozco, N., and von Boehmer, H. (2003). Normal incidence of diabetes in NOD mice tolerant to glutamic acid decarboxylase. J Exp Med 197:1635-1644.
PMID: 12796471, https://www.ncbi.nlm.nih.gov/pubmed/12796471

2002

Kyewski, B., Derbinski, J., Gotter, J., and Klein, L. (2002). Promiscuous gene expression and central T-cell tolerance: more than meets the eye. Trends Immunol 23:364-371.
PMID: 12103357, https://www.ncbi.nlm.nih.gov/pubmed/12103357

Jansson, M., Panoutsakopoulou, V., Baker, J., Klein, L., and Cantor, H. (2002). Cutting edge: Attenuated experimental autoimmune encephalomyelitis in eta-1/osteopontin-deficient mice. J Immunol 168:2096-2099.
PMID: 11859094, https://www.ncbi.nlm.nih.gov/pubmed/11859094

Gounari, F., Signoretti, S., Bronson, R., Klein, L., Sellers, W.R., Kum, J., Siermann, A., Taketo, M.M., von Boehmer, H., and Khazaie, K. (2002). Stabilization of beta-catenin induces lesions reminiscent of prostatic intraepithelial neoplasia, but terminal squamous transdifferentiation of other secretory epithelia. Oncogene 21:4099-4107.
PMID: 12037666, https://www.ncbi.nlm.nih.gov/pubmed/12037666

Apostolou, I., Sarukhan, A., Klein, L., and von Boehmer, H. (2002). Origin of regulatory T cells with known specificity for antigen. Nat Immunol 3:756-763.
PMID: 12089509, https://www.ncbi.nlm.nih.gov/pubmed/12089509

Anderson, M.S., Venanzi, E.S., Klein, L., Chen, Z., Berzins, S.P., Turley, S.J., von Boehmer, H., Bronson, R., Dierich, A., Benoist, C., and Mathis, D. (2002). Projection of an immunological self shadow within the thymus by the aire protein. Science 298:1395-1401.
PMID: 12376594, https://www.ncbi.nlm.nih.gov/pubmed/12376594

2001

Klein, L., Roettinger, B., and Kyewski, B. (2001). Sampling of complementing self-antigen pools by thymic stromal cells maximizes the scope of central T cell tolerance. Eur J Immunol 31:2476-2486.
PMID: 11500832, https://www.ncbi.nlm.nih.gov/pubmed/11500832

Derbinski, J., Schulte, A., Kyewski, B., and Klein, L. (2001). Promiscuous gene expression in medullary thymic epithelial cells mirrors the peripheral self. Nat Immunol 2:1032-1039.
PMID: 11600886, https://www.ncbi.nlm.nih.gov/pubmed/11600886

2000

Kyewski, B., Rottinger, B., and Klein, L. (2000). Making central T-cell tolerance efficient: thymic stromal cells sample distinct self-antigen pools. Curr Top Microbiol Immunol 251:139-145.
PMID: 11036769, https://www.ncbi.nlm.nih.gov/pubmed/11036769

Klein, L., and Kyewski, B. (2000a). "Promiscuous" expression of tissue antigens in the thymus: a key to T-cell tolerance and autoimmunity? J Mol Med (Berl) 78:483-494.
PMID: 11140374, https://www.ncbi.nlm.nih.gov/pubmed/11140374

Klein, L., and Kyewski, B. (2000b). Self-antigen presentation by thymic stromal cells: a subtle division of labor. Curr Opin Immunol 12:179-186.
PMID: 10712940, https://www.ncbi.nlm.nih.gov/pubmed/10712940

Klein, L., Klugmann, M., Nave, K.A., Tuohy, V.K., and Kyewski, B. (2000). Shaping of the autoreactive T-cell repertoire by a splice variant of self protein expressed in thymic epithelial cells. Nat Med 6:56-61.
PMID: 10613824, https://www.ncbi.nlm.nih.gov/pubmed/10613824

1993-2000

Klein, L., Klein, T., Ruther, U., and Kyewski, B. (1998). CD4 T cell tolerance to human C-reactive protein, an inducible serum protein, is mediated by medullary thymic epithelium. J Exp Med 188:5-16.
PMID: 9653079, https://www.ncbi.nlm.nih.gov/pubmed/9653079

Tourne, S., Miyazaki, T., Oxenius, A., Klein, L., Fehr, T., Kyewski, B., Benoist, C., and Mathis, D. (1997). Selection of a broad repertoire of CD4+ T cells in H-2Ma0/0 mice. Immunity 7:187-195.
PMID: 9285404, https://www.ncbi.nlm.nih.gov/pubmed/9285404

da Costa e Silva, O., Klein, L., Schmelzer, E., Trezzini, G.F., and Hahlbrock, K. (1993). BPF-1, a pathogen-induced DNA-binding protein involved in the plant defense response. Plant J 4:125-135.
PMID: 8220470, https://www.ncbi.nlm.nih.gov/pubmed/8220470