Systems biology approaches for understanding cellular mechanisms of immunity in lymph nodes during infection

Journal of Theoretical Biology

Volumn 287, Issue 1, 2011, Pages 160-170

  Mirsky, Henry P ^a   Miller, Mark J ^c   Linderman, Jennifer J ^a   Kirschner, Denise E ^b  

^a UNIVERSITY OF MICHIGAN   (United States)

^b UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

^c WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Agent based models; Cellular Potts models; Dendritic cells; Markov models; Two photon microscopy

Indexed keywords

ANTIGEN; CELL ORGANELLE; IMMUNITY; MARKOV CHAIN; NUMERICAL MODEL; PEPTIDE;

CELL FUNCTION; CELL INTERACTION; CELL MOTION; CELLULAR DISTRIBUTION; CELLULAR IMMUNITY; DENDRITIC CELL; HOST PATHOGEN INTERACTION; HUMAN; INFECTION; LYMPH NODE; LYMPHOCYTE STRUCTURE; NEUROANATOMY; NONHUMAN; PRIORITY JOURNAL; REVIEW; SYSTEMS BIOLOGY; T LYMPHOCYTE; T LYMPHOCYTE ACTIVATION;

ADAPTIVE IMMUNITY; ANIMALS; COMMUNICABLE DISEASES; DENDRITIC CELLS; HUMANS; LYMPH NODES; MODELS, IMMUNOLOGICAL; SYSTEMS BIOLOGY; T-LYMPHOCYTES;

EID: 81155159689     PISSN: 00225193     EISSN: 10958541     Source Type: Journal    
DOI: 10.1016/j.jtbi.2011.06.037     Document Type: Review

References (106)

1. Anderson A.O., Shaw S. T cell adhesion to endothelium: The FRC conduit system and other anatomic and molecular features which facilitate the adhesion cascade in lymph node. Semin. Immunol 1993, 5(4):271-282.
2. Agrawal N.G., Linderman J.J. Calcium response of helper T lymphocytes to antigen-presenting cells in a single-cell assay. Biophys. J. 1995, 69:1178-1190.
3. Aoshi T., Zinselmeyer B.H., Konjufca V., Lynch J.N., Zhang X., Koide Y., Miller M.J. Bacterial entry to the splenic white pulp initiates antigen presentation to CD8+ T cells. Immunity 2008, 29:476-486.
4. Arstila T.P., Casrouge A., Baron V., Even J., Kanellopoulos J., Kourilsky P. A direct estimate of the human alphabeta T cell receptor diversity. Science 1999, 286(5441):958-961.
5. Bajaria S.H., Webb G., Cloyd M., Kirschner D. Dynamics of naive and memory CD4+ T lymphocytes in HIV-1 disease progression. J. Acquir. Immune Defic. Syndr. 2002, 30:41-58.
6. Bajenoff M., Egen J.G., Koo L.Y., Laugier J.P., Brau F., Glaichenhaus N., Germain R.N. Stromal cell networks regulate lymphocyte entry, migration, and territoriality in lymph nodes. Immunity 2006, 25:989-1001.
7. Baldazzi V., Paci P., Bernaschi M., Castiglione F. Modeling lymphocyte homing and encounters in lymph nodes. BMC Bioinformatics 2009, 10:387.
8. Bauer A.L., Beauchemin C.A., Perelson A.S. Agent-based modeling of host-pathogen systems: The successes and challenges. Inf. Sci. (Ny) 2009, 179:1379-1389.
9. Beauchemin C., Dixit N.M., Perelson A.S. Characterizing T cell movement within lymph nodes in the absence of antigen. J. Immunol. 2007, 178:5505-5512.
10. Beltman J.B., Henrickson S.E., von Andrian U.H., de Boer R.J., Maree A.F. Towards estimating the true duration of dendritic cell interactions with T cells. J. Immunol. Methods 2009, 347:54-69.
11. Beltman J.B., Maree A.F., de Boer R.J. Spatial modelling of brief and long interactions between T cells and dendritic cells. Immunol. Cell Biol. 2007, 85:306-314.
12. Beltman J.B., Maree A.F., Lynch J.N., Miller M.J., de Boer R.J. Lymph node topology dictates T cell migration behavior. J. Exp. Med. 2007, 204:771-780.
13. Beuneu H., Garcia Z., Bousso P. Cutting edge: cognate CD4 help promotes recruitment of antigen-specific CD8 T cells around dendritic cells. J. Immunol. Aug 1 2006, 177(3):1406-1410.
14. Blattman J.N., Antia R., Sourdive D.J., Wang X., Kaech S.M., Murali-Krishna K., Altman J.D., Ahmed R. Estimating the precursor frequency of naive antigen-specific CD8 T cells. J. Exp. Med. 2002, 195:657-664.
15. Bogle G., Dunbar P.R. Agent-based simulation of T-cell activation and proliferation within a lymph node. Immunol. Cell Biol 2010, 88:172-179.
16. Bogle G., Dunbar P.R. T cell responses in lymph nodes. Wiley Interdiscip. Rev. Syst. Biol. Med. 2010, 2:107-116.
17. Bogle G., Dunbar P.R. Simulating T-cell motility in the lymph node paracortex with a packed lattice geometry. Immunol. Cell Biol. 2008, 86:676-687.
18. Bousso P., Robey E. Dynamics of CD8+ T cell priming by dendritic cells in intact lymph nodes. Nat. Immunol. 2003, 4:579-585.
19. Cahill R.N., Frost H., Trnka Z. The effects of antigen on the migration of recirculating lymphocytes through single lymph nodes. J. Exp. Med. 1976, 143:870-888.
20. Casrouge A., Beaudoing E., Dalle S., Pannetier C., Kanellopoulos J., Kourilsky P. Size estimate of the alpha beta TCR repertoire of naive mouse splenocytes. J. Immunol. 2000, 164:5782-5787.
21. Castellino F., Huang A.Y., Altan-Bonnet G., Stoll S., Scheinecker C., Germain R.N. Chemokines enhance immunity by guiding naive CD8+ T cells to sites of CD4+ T cell-dendritic cell interaction. Nature 2006, 440:890-895.
22. Catron D.M., Itano A.A., Pape K.A., Mueller D.L., Jenkins M.K. Visualizing the first 50 hr of the primary immune response to a soluble antigen. Immunity 2004, 21:341-347.
23. Celada F., Seiden P.E. A computer model of cellular interactions in the immune system. Immunol. Today 1992, 13:56-62.
24. Celli S., Lematre F., Bousso P. Real-time manipulation of T cell-dendritic cell interactions in vivo reveals the importance of prolonged contacts for CD4+ T cell activation. Immunity Oct 2007, 27(4):625-634.
25. Celli S., Garcia Z., Beuneu H., Bousso P. Decoding the dynamics of T cell-dendritic cell interactions in vivo. Immunol. Rev. 2008, 221:182-187.
26. Chang S.T., Linderman J.J., Kirschner D.E. Multiple mechanisms allow Mycobacterium tuberculosis to continuously inhibit MHC class II-mediated antigen presentation by macrophages. Proc. Natl. Acad. Sci. USA 2005, 102:4530-4535.
27. Chyou S., Ekland E.H., Carpenter A.C., Tzeng T.C., Tian S., Michaud M., Madri J.A., Lu T.T. Fibroblast-type reticular stromal cells regulate the lymph node vasculature. J. Immunol. 2008, 181:3887-3896.
28. Coombs D., Kalergis A.M., Nathenson S.G., Wofsy C., Goldstein B. Activated TCRs remain marked for internalization after dissociation from pMHC. Nat. Immunol. 2002, 3:926-931.
29. DeFea K.A. Stop that cell! beta-arrestin-dependent chemotaxis: A tale of localized actin assembly and receptor desensitization. Annu. Rev. Physiol. 2007, 69:535-560.
30. Demotz S., Grey H.M., Sette A. The minimal number of class II MHC-antigen complexes needed for T cell activation. Science 1990, 249:1028-1030.
31. Diedrich C.R., Mattila J.T., Klein E., Janssen C., Phuah J., Sturgeon T.J., Montelaro R.C., Lin P.L., Flynn J.L. Reactivation of latent tuberculosis in cynomolgus macaques infected with SIV is associated with early peripheral T cell depletion and not virus load. PLoS One 2010, 5:e9611.
32. Egen J.G., Rothfuchs A.G., Feng C.G., Winter N., Sher A., Germain R.N. Macrophage and T cell dynamics during the development and disintegration of mycobacterial granulomas. Immunity 2008, 28:271-284.
33. Engelmayer J., Larsson M., Subklewe M., Chahroudi A., Cox W.I., Steinman R.M., Bhardwaj N. Vaccinia virus inhibits the maturation of human dendritic cells: a novel mechanism of immune evasion. J. Immunol. 1999, 163:6762-6768.
34. Fallahi-Sichani M., El-Kebir M., Marino S., Kirschner D.E., Linderman J.J. Multiscale computational modeling reveals a critical role for TNF-{alpha} receptor 1 dynamics in Tuberculosis Granuloma Formation. J. Immunol 2011.
35. Fallahi-Sichani M., Schaller M.A., Kirschner D.E., Kunkel S.L., Linderman J.J. Identification of key processes that control tumor necrosis factor availability in a tuberculosis granuloma. PLoS Comput. Biol. 2010, 6:e1000778.
36. Figge M.T., Meyer-Hermann M. Modeling receptor-ligand binding kinetics in immunological synapse formation. Eur. Phys. J. D 2009, 51:153-160.
37. Ford W.L., Simmonds S.J. The tempo of lymphocyte recirculation from blood to lymph in the rat. Cell Tissue Kinet 1972, 5:175-189.
38. Glazier J.A., Graner F. Simulation of the differential adhesion driven rearrangement of biological cells. Phys. Rev. E Stat. Phys. Plasmas Fluids Relat. Interdiscip. Top. 1993, 47:2128-2154.
39. Gonzalez P.A., Carreno L.J., Coombs D., Mora J.E., Palmieri E., Goldstein B., Nathenson S.G., Kalergis A.M. T cell receptor binding kinetics required for T cell activation depend on the density of cognate ligand on the antigen-presenting cell. Proc. Natl. Acad. Sci. USA 2005, 102:4824-4829.
40. Gowans J.L. The recirculation of lymphocytes from blood to lymph in the rat. J. Physiol. 1959, 146:54-69.
41. Graner F., Glazier J.A. Simulation of biological cell sorting using a two-dimensional extended Potts model. Phys. Rev. Lett. 1992, 69:2013-2016.
42. Grigorova I.L., Panteleev M., Cyster J.G. Lymph node cortical sinus organization and relationship to lymphocyte egress dynamics and antigen exposure. Proc. Natl. Acad. Sci. USA 2010, 107:20447-20452.
43. Grigorova I.L., Schwab S.R., Phan T.G., Pham T.H., Okada T., Cyster J.G. Cortical sinus probing, S1P1-dependent entry and flow-based capture of egressing T cells. Nat. Immunol. 2009, 10:58-65.
44. Hall J., Scollay R., Smith M. Studies on the lymphocytes of sheep. I. Recirculation of lymphocytes through peripheral lymph nodes and tissues. Eur. J. Immunol. 1976, 6:117-120.
45. Harding C.V., Ramachandra L., Wick M.J. Interaction of bacteria with antigen presenting cells: Influences on antigen presentation and antibacterial immunity. Curr. Opin. Immunol. 2003, 15:112-119.
46. Harding C.V., Unanue E.R. Quantitation of antigen-presenting cell MHC class II/peptide complexes necessary for T-cell stimulation. Nature 1990, 346:574-576.
47. Hay J.B., Hobbs B.B. The flow of blood to lymph nodes and its relation to lymphocyte traffic and the immune response. J. Exp. Med. 1977, 145:31-44.
48. Hmama Z., Gabathuler R., Jefferies W.A., de Jong G., Reiner N.E. Attenuation of HLA-DR expression by mononuclear phagocytes infected with Mycobacterium tuberculosis is related to intracellular sequestration of immature class II heterodimers. J. Immunol. 1998, 161:4882-4893.
49. Jain R.K. Molecular regulation of vessel maturation. Nat. Med. 2003, 9:685-693.
50. Kirschner D.E. The Multi-scale Immune Response to Pathogens: M. tuberculosis as an Example. In In Silico Immunology 2007, Springer, US, pp. 289-311.
51. Kirschner D.E., Chang S.T., Riggs T.W., Perry N., Linderman J.J. Toward a multiscale model of antigen presentation in immunity. Immunol. Rev. 2007, 216:93-118.
52. Kirschner D.E., Linderman J.J. Mathematical and computational approaches can complement experimental studies of host-pathogen interactions. Cell. Microbiol. 2009, 11:531-539.
53. Konjufca V., Miller M.J. Two-photon microscopy of host-pathogen interactions: Acquiring a dynamic picture of infection in vivo. Cell Microbiol. 2009, 11(4):551-559.
54. Lin J., Miller M.J., Shaw A.S. The c-SMAC: Sorting it all out (or in). J. Cell Biol. 2005 Jul 18 2005, 170(2):177-182.
55. Linderman J.J., Riggs T., Pande M., Miller M., Marino S., Kirschner D.E. Characterizing the dynamics of CD4+ T cell priming within a lymph node. J. Immunol. 2010, 184:2873-2885.
56. Lo C.G., Xu Y., Proia R.L., Cyster J.G. Cyclical modulation of sphingosine-1-phosphate receptor 1 surface expression during lymphocyte recirculation and relationship to lymphoid organ transit. J. Exp. Med. 2005, 201:291-301.
57. Marino S., Hogue I.B., Ray C.J., Kirschner D.E. A methodology for performing global uncertainty and sensitivity analysis in systems biology. J. Theor. Biol. 2008, 254:178-196.
58. Marino S., Linderman J.J., Kirschner D.E. A multifaceted approach to modeling the immune response in tuberculosis. Wiley Interdiscip. Rev. Syst. Biol. Med. 2010.
59. Marino S., Myers A., Flynn J.L., Kirschner D.E. TNF and IL-10 are major factors in modulation of the phagocytic cell environment in lung and lymph node in tuberculosis: A next-generation two-compartmental model. J. Theor. Biol. 2010, 265:586-598.
60. Marino S., Pawar S., Fuller C.L., Reinhart T.A., Flynn J.L., Kirschner D.E. Dendritic cell trafficking and antigen presentation in the human immune response to Mycobacterium tuberculosis. J. Immunol. 2004, 173:494-506.
61. Matloubian M., Lo C.G., Cinamon G., Lesneski M.J., Xu Y., Brinkmann V., Allende M.L., Proia R.L., Cyster J.G. Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1. Nature 2004, 427:355-360.
62. Mazzaccaro R.J., Gedde M., Jensen E.R., van Santen H.M., Ploegh H.L., Rock K.L., Bloom B.R. Major histocompatibility class I presentation of soluble antigen facilitated by Mycobacterium tuberculosis infection. Proc. Natl. Acad. Sci. USA 1996, 93:11786-11791.
63. McFadden G., Murphy P.M. Host-related immunomodulators encoded by poxviruses and herpesviruses. Curr. Opin. Microbiol. 2000, 3:371-378.
64. Meier-Schellersheim M., Xu X., Angermann B., Kunkel E.J., Jin T., Germain R.N. Key role of local regulation in chemosensing revealed by a new molecular interaction-based modeling method. PLoS Comput. Biol. 2006, 2:e82.
65. Mempel T.R., Henrickson S.E., Von Andrian U.H. T-cell priming by dendritic cells in lymph nodes occurs in three distinct phases. Nature 2004, 427:154-159.
66. Meyer-Hermann M.E., Maini P.K. Interpreting two-photon imaging data of lymphocyte motility. Phys. Rev. E. Stat. Nonlinear Soft Matter Phys. 2005, 71:061912.
67. Miller M.J. MJ Miller's introduction for the seminars in immunopathology special issue on two-photon imaging immunity. Semin. Immunopathol. 2010, 32(3):211-213.
68. Miller M.J., Hejazi A.S., Wei S.H., Cahalan M.D., Parker I. T cell repertoire scanning is promoted by dynamic dendritic cell behavior and random T cell motility in the lymph node. Proc. Natl. Acad. Sci. USA 2004, 101:998-1003.
69. Miller M.J., Safrina O., Parker I., Cahalan M.D. Imaging the single cell dynamics of CD4+ T cell activation by dendritic cells in lymph nodes. J. Exp. Med. 2004, 200:847-856.
70. Miller M.J., Wei S.H., Cahalan D., Parker I. Autonomous T cell trafficking examined in vivo with intravital two-photon microscopy. Proc. Natl. Acad. Sci. USA 2003, 100(5):2604-2609. (PMID 12601158).
71. Miller M.J., Wei S.H., Parker I., Cahalan M.D. Two-photon imaging of lymphocyte motility and antigen response in intact lymph node. Science 2002, 296:1869-1873.
72. Moreno C., Mehlert A., Lamb J. The inhibitory effects of mycobacterial lipoarabinomannan and polysaccharides upon polyclonal and monoclonal human T cell proliferation. Clin. Exp. Immunol 1988, 74:206-210.
73. Mueller S.N., Germain R.N. Stromal cell contributions to the homeostasis and functionality of the immune system. Nat. Rev. Immunol. 2009, 9:618-629.
74. Naylor K., Li G., Vallejo A.N., Lee W.W., Koetz K., Bryl E., Witkowski J., Fulbright J., Weyand C.M., Goronzy J.J. The influence of age on T cell generation and TCR diversity. J. Immunol. 2005, 174(11):7446-7452.
75. Noss E.H., Harding C.V., Boom W.H. Mycobacterium tuberculosis inhibits MHC class II antigen processing in murine bone marrow macrophages. Cell Immunol. 2000, 201:63-74.
76. Okada T., Cyster J.G. CC chemokine receptor 7 contributes to Gi-dependent T cell motility in the lymph node. J. Immunol. 2007, 178:2973-2978.
77. Pham T.H., Okada T., Matloubian M., Lo C.G., Cyster J.G. S1P1 receptor signaling overrides retention mediated by G alpha i-coupled receptors to promote T cell egress. Immunity 2008, 28:122-133.
78. Preston S.P., Waters S.L., Jensen O.E., Heaton P.R., Pritchard D.I. T-cell motility in the early stages of the immune response modeled as a random walk amongst targets. Phys. Rev. E. Stat. Nonlinear Soft Matter Phys. 2006, 74:011910.
79. Randolph G.J., Angeli V., Swartz M.A. Dendritic-cell trafficking to lymph nodes through lymphatic vessels. Nat. Rev. Immunol. 2005, 5:617-628.
80. Riggs T., Walts A., Perry N., Bickle L., Lynch J.N., Myers A., Flynn J., Linderman J.J., Miller M.J., Kirschner D.E. A comparison of random vs. chemotaxis-driven contacts of T cells with dendritic cells during repertoire scanning. J. Theor. Biol. 2008, 250:732-751.
81. Sage P.T., Carman C.V. Settings and mechanisms for trans-cellular diapedesis. Front. Biosci. 2009, 14:5066-5083.
82. Sallusto F., Schaerli P., Loetscher P., Schaniel C., Lenig D., Mackay C.R., Qin S., Lanzavecchia A. Rapid and coordinated switch in chemokine receptor expression during dendritic cell maturation. Eur. J. Immunol. 1998, 28:2760-2769.
83. Sathaliyawala T., O'Gorman W.E., Greter M., Bogunovic M., Konjufca V., Hou Z.E., Nolan G.P., Miller M.J., Merad M., Reizis B. Mammalian target of rapamycin controls dendritic cell development downstream of Flt3 ligand signaling. Immunity 2010, 33:597-606.
84. Shakhar G., Lindquist R.L., Skokos D., Dudziak D., Huang J.H., Nussenzweig M.C., Dustin M.L. Stable T cell-dendritic cell interactions precede the development of both tolerance and immunity in vivo. Nat Immunol. Jul 2005, 6(7):707-714.
85. Sinha R.K., Park C., Hwang I.Y., Davis M.D., Kehrl J.H. B lymphocytes exit lymph nodes through cortical lymphatic sinusoids by a mechanism independent of sphingosine-1-phosphate-mediated chemotaxis. Immunity 2009, 30:434-446.
86. Smith M.E., Ford W.L. The recirculating lymphocyte pool of the rat: A systematic description of the migratory behaviour of recirculating lymphocytes. Immunology 1983, 49:83-94.
87. Soderberg K.A., Payne G.W., Sato A., Medzhitov R., Segal S.S., Iwasaki A. Innate control of adaptive immunity via remodeling of lymph node feed arteriole. Proc. Natl. Acad. Sci. USA 2005, 102:16315-16320.
88. Steeber D.A., Erickson C.M., Hodde K.C., Albrecht R.M. Vascular changes in popliteal lymph nodes due to antigen challenge in normal and lethally irradiated mice. Scanning Microsc. 1987, 1:831-839.
89. Tomura M., Yoshida N., Tanaka J., Karasawa S., Miwa Y., Miyawaki A., Kanagawa O. Monitoring cellular movement in vivo with photoconvertible fluorescence protein "Kaede" transgenic mice. Proc. Natl. Acad. Sci. USA 2008, 105:10871-10876.
90. Tortorella D., Gewurz B.E., Furman M.H., Schust D.J., Ploegh H.L. Viral subversion of the immune system. Annu. Rev. Immunol. 2000, 18:861-926.
91. von Andrian U.H., Mempel T.R. Homing and cellular traffic in lymph nodes. Nat. Rev. Immunol. 2003, 3:867-878.
92. Waite J., Leirner I., Lauer P., Rae C.S., Barbet G., Zheng H., Portnoy D.A., Pamer E.G., Dustin M.L. Dynamic imaging of the effector immune response to Listeria infection in vivo. PLoS Pathog. 2011, 7(3):e1001326.
93. Webster B., Ekland E.H., Agle L.M., Chyou S., Ruggieri R., Lu T.T. Regulation of lymph node vascular growth by dendritic cells. J. Exp. Med. 2006, 203:1903-1913.
94. Wei S.H., Parker I., Miller M.J., Cahalan M.D. A stochastic view of lymphocyte motility and trafficking within the lymph node. Immunol. Rev. 2003, 195:136-159.
95. Wei S.H., Rosen H., Matheu M.P., Sanna M.G., Wang S.K., Jo E., Wong C.H., Parker I., Cahalan M.D. Sphingosine 1-phosphate type 1 receptor agonism inhibits transendothelial migration of medullary T cells to lymphatic sinuses. Nat. Immunol. 2005, 6:1228-1235.
96. Weisstein, Eric W. 2011. "Moore Neighborhood." From MathWorld-A Wolfram Web Resource. http://mathworld.wolfram.com/MooreNeighborhood.html.
97. Westermann J., Persin S., Matyas J., van der Meide P., Pabst R. IFN-gamma influences the migration of thoracic duct B and T lymphocyte subsets in vivo. Random increase in disappearance from the blood and differential decrease in reappearance in the lymph. J. Immunol. 1993, 150:3843-3852.
98. Westermann J., Puskas Z., Pabst R. Blood transit and recirculation kinetics of lymphocyte subsets in normal rats. Scand. J. Immunol. 1988, 28:203-210.
99. Worbs T., Forster R. T cell migration dynamics within lymph nodes during steady state: An overview of extracellular and intracellular factors influencing the basal intranodal T cell motility. Curr. Top. Microbiol. Immunol 2009, 334:71-105.
100. Worbs T., Mempel T.R., Bolter J., von Andrian U.H., Forster R. CCR7 ligands stimulate the intranodal motility of T lymphocytes in vivo. J. Exp. Med. 2007, 204:489-495.
101. Wylie D.C., Das J., Chakraborty A.K. Sensitivity of T cells to antigen and antagonism emerges from differential regulation of the same molecular signaling module. Proc. Natl. Acad. Sci. USA 2007, 104:5533-5538.
102. Young D., Stark J., Kirschner D. Systems biology of persistent infection: Tuberculosis as a case study. Nat. Rev. Microbiol. 2008, 6:520-528.
103. Yrlid U., Svensson M., Kirby A., Wick M.J. Antigen-presenting cells and anti-Salmonella immunity. Microbes Infect. 2001, 3:1239-1248.
104. Yrlid U., Wick M.J. Salmonella-induced apoptosis of infected macrophages results in presentation of a bacteria-encoded antigen after uptake by bystander dendritic cells. J. Exp. Med. 2000, 191:613-624.
105. Zheng H., Jin B., Henrickson S.E., Perelson A.S., von Andrian U.H., Chakraborty A.K. How antigen quantity and quality determine T-cell decisions in lymphoid tissue. Mol. Cell. Biol. 2008, 28:4040-4051.
106. Zinselmeyer B.H., Dempster J., Gurney A.M., Wokosin D., Miller M., Ho H., Millington O.R., Smith K.M., Rush C.M., Parker I., Cahalan M., Brewer J.M., Garside P. In situ characterization of CD4+T cell behavior in mucosal and systemic lymphoid tissues during the induction of oral priming and tolerance. J Exp. Med. Jun 6 2005, 201(11):1815-1823.