Crossref journal-article
Wiley
Immunological Reviews (311)
Abstract

Summary: T cells undergo a defined program of phenotypic and genetic changes during differentiation within the thymus. These changes define commitment of T‐cell receptor (TCR)γσ and TCRαβ cells and lineage differentiation into CD4+ T helper and CD8+ cytotoxic T cells, T‐cell differentiation and selection in the thymus constitute a tightly co‐ordinated multistep journey through a network that can be envisaged as a three‐dimensional informational highway made up of stromal cells and extracellular matrix molecules. This intrathymic journey is controlled by information exchange, with thymocytes depending on two‐way cellular interactions with thymic stromal cells in order to receive essential signals for maturation and selection. Genetic inactivation of surface receptors, signal transduction molecules, and transcription factors using homologous recombination has provided novel insight into the signaling cascades that relay surface receptor engagement to gene transcription and subsequent progression of the developmental program. In this review we discuss molecular mechanisms of T lymphocyte development in mice that harbour genetic mutations in the guanine nucleotide exchange factor Vav and the interferon regulatory transcription factor 1 (IRF‐1). We also propose a novel model of T‐cell selection based on TCRα chain‐directed signals for allelic exclusion and TCRα‐based selection for single receptor usage.

Bibliography

Penninger, J. M., & Mak, T. W. (1998). Thymocyte selection in Vav and IRF‐1 gene‐deficient mice. Immunological Reviews, 165(1), 149–166. Portico.

Authors 2
  1. Josef M. Penninger (first)
  2. Tak W. Mak (additional)
References 213 Referenced 9
  1. 10.1016/0952-7915(92)90003-W
  2. 10.1126/science.280.5361.237
  3. 10.1084/jem.179.4.1355
  4. 10.1038/375795a0
  5. 10.1126/science.7973703
  6. 10.1007/BF00176445
  7. 10.1016/S0952-7915(97)80146-X
  8. 10.1146/annurev.immunol.15.1.433
  9. 10.1084/jem.182.1.121
  10. 10.1126/science.280.5365.905
  11. 10.1126/science.8493533
  12. 10.1016/0167-5699(89)90307-1
  13. 10.1084/jem.183.3.713
  14. 10.1016/0092-8674(87)90568-X
  15. 10.1111/j.1600-065X.1988.tb00737.x
  16. 10.1016/0167-5699(91)90161-L
  17. 10.1016/0167-5699(93)90248-J
  18. 10.1126/science.8128249
  19. 10.1084/jem.183.3.1093
  20. 10.1016/0092-8674(94)90169-4
  21. 10.1126/science.8171333
  22. 10.1016/0092-8674(94)90505-3
  23. 10.1084/jem.178.2.615
  24. 10.1016/S0167-5699(97)01037-2
  25. 10.1038/356068a0
  26. 10.1038/356071a0
  27. 10.1002/j.1460-2075.1989.tb08354.x
  28. 10.1074/jbc.271.42.25731
  29. 10.1074/jbc.270.10.5620
  30. 10.1016/S0955-0674(97)80156-1
  31. 10.1016/S0092-8674(05)80019-4
  32. 10.1126/science.7618083
  33. 10.1016/S0960-9822(97)70091-5
  34. 10.1128/MCB.14.2.906
  35. 10.1126/science.8484124
  36. 10.1038/385169a0
  37. 10.1128/MCB.17.3.1346
  38. {'key': 'e_1_2_1_39_2', 'first-page': '455', 'article-title': 'Rac‐1 dependent stimulation of the JNK/SAPK signaling pathway by Vav', 'volume': '13', 'author': 'Crespo R', 'year': '1996', 'journal-title': 'Oncogene'} / Oncogene / Rac‐1 dependent stimulation of the JNK/SAPK signaling pathway by Vav by Crespo R (1996)
  39. 10.1084/jem.184.3.1161
  40. 10.1016/S1074-7613(00)80422-7
  41. 10.1016/S1074-7613(00)80485-9
  42. 10.1002/j.1460-2075.1995.tb06969.x
  43. 10.1016/S0960-9822(98)70224-6
  44. 10.1016/S1074-7613(00)80367-2
  45. 10.1038/374470a0
  46. 10.1038/374474a0
  47. 10.1038/374467a0
  48. 10.1084/jem.185.6.981
  49. 10.1038/376352a0
  50. 10.1016/1074-7613(95)90157-4
  51. 10.1073/pnas.94.24.13152
  52. 10.1016/1074-7613(95)90114-0
  53. 10.1046/j.1365-3083.1997.d01-447.x
  54. 10.1016/S0021-9258(18)31664-8 / J Biol Chem / Signaling through CD 19 activates Vav/mitogen‐activated protein kinase pathway and induces formation of a CD19/Vav/phosphatidyl‐inositol 3‐kinase complex in human B cell precursors by Weng WK (1994)
  55. 10.1016/S1074-7613(00)80568-3
  56. 10.1016/S0092-8674(00)81422-1
  57. 10.1126/science.281.5375.416
  58. 10.1111/j.1469-1809.1995.tb01603.x
  59. {'key': 'e_1_2_1_60_2', 'first-page': '363', 'article-title': 'Isolation and characterization of murine vav2. a member of the vav family of proto‐oncogenes', 'volume': '13', 'author': 'Schuebel KE', 'year': '1996', 'journal-title': 'Oncogene'} / Oncogene / Isolation and characterization of murine vav2. a member of the vav family of proto‐oncogenes by Schuebel KE (1996)
  60. 10.1038/357161a0
  61. 10.1126/science.8469988
  62. 10.1016/0092-8674(92)90309-Z
  63. 10.1016/0092-8674(92)90308-Y
  64. 10.1016/S1074-7613(00)80498-7
  65. 10.1016/S1074-7613(00)80499-9
  66. 10.1073/pnas.94.18.9797
  67. 10.1038/376435a0
  68. 10.1038/378298a0
  69. 10.1038/378303a0
  70. 10.1073/pnas.93.18.9704
  71. 10.1084/jem.183.4.1707
  72. {'key': 'e_1_2_1_73_2', 'first-page': '143', 'article-title': 'Normal B lymphocyte development but impaired T cell maturation in GD45‐exon6 protein tyrosine phosphatase‐deficient mice', 'volume': '74', 'author': 'Kishihara K', 'year': '1993', 'journal-title': 'Gell'} / Gell / Normal B lymphocyte development but impaired T cell maturation in GD45‐exon6 protein tyrosine phosphatase‐deficient mice by Kishihara K (1993)
  73. 10.4049/jimmunol.158.7.3130 / J Immunol / T cell development in mice expressing splice variants of the protein tyrosine phosphatase CD45 by Kozieradzki I (1997)
  74. 10.1038/335229a0
  75. 10.1002/j.1460-2075.1989.tb03431.x / EMBO J / T cell tolerance to Mlsa encoded antigens in T ceil receptor V β 8.1chain transgenic mice by Pircher H (1989)
  76. {'key': 'e_1_2_1_77_2', 'article-title': 'Vav regulates peptide‐specific apoptosis in thymocytes', 'author': 'Kong YY', 'journal-title': 'J Exp Med'} / J Exp Med / Vav regulates peptide‐specific apoptosis in thymocytes by Kong YY
  77. 10.1016/S0065-2776(08)60558-1
  78. 10.1084/jem.184.4.1331
  79. 10.1084/jem.183.4.1533
  80. 10.1126/science.275.5303.1129
  81. 10.1016/S0092-8674(00)80085-9
  82. 10.1126/science.275.5303.1132
  83. 10.1084/jem.182.2.367
  84. 10.1084/jem.186.9.1503
  85. 10.1016/S0960-9822(98)70225-8
  86. 10.1016/0092-8674(85)90183-7
  87. 10.1084/jem.181.2.577
  88. 10.1126/science.278.5336.294
  89. 10.1093/emboj/16.15.4650
  90. 10.1021/bi9711487
  91. 10.1083/jcb.139.3.759
  92. 10.1126/science.276.5318.1571
  93. 10.1242/jcs.111.6.713 / J Cell Sci / Calpain inhibitors, but not caspase inhibitors, prevent actin proteolysis and DNA fragmentation during apoptosis by Villa PG (1998)
  94. {'key': 'e_1_2_1_95_2', 'first-page': '379', 'article-title': "Antibody to caspase‐cleaved actin detects apoptosis in differentiated neuroblastoma and plaque‐associated neurons and microglia in Alzheimer's disease", 'volume': '152', 'author': 'Yang ES', 'year': '1998', 'journal-title': 'Am J Pathol'} / Am J Pathol / Antibody to caspase‐cleaved actin detects apoptosis in differentiated neuroblastoma and plaque‐associated neurons and microglia in Alzheimer's disease by Yang ES (1998)
  95. 10.1038/34214
  96. 10.1523/JNEUROSCI.17-14-05316.1997 / J Neurosci / Thrombin induces apoptosis in cultured neurons and astrocytes via a pathway requiring tyrosine kinase and Rho A activities by Donovan FM (1997)
  97. 10.1042/bj3230233
  98. 10.1038/sj.onc.1200919
  99. 10.1073/pnas.93.5.2234
  100. 10.1002/j.1460-2075.1995.tb00202.x
  101. 10.1074/jbc.270.12.6425
  102. 10.1128/MCB.14.10.6848
  103. 10.1016/S0960-9822(02)70786-0
  104. 10.1038/385350a0
  105. 10.1084/jem.186.6.941
  106. 10.1126/science.279.5350.558
  107. 10.1084/jem.186.11.1911
  108. 10.1096/fasebj.11.8.9240967
  109. {'key': 'e_1_2_1_110_2', 'first-page': '829', 'article-title': 'Protein kinase C and tumorigenic potential', 'volume': '84', 'author': 'BaronDelage S', 'year': '1997', 'journal-title': 'Bull Cancer'} / Bull Cancer / Protein kinase C and tumorigenic potential by BaronDelage S (1997)
  110. 10.1096/fasebj.12.1.35 / FASEB J / Anchoring proteins for protein kinase C: a means for isozyme selectivity by MochlyRosen D (1998)
  111. 10.1111/j.1432-1033.1994.00195.x
  112. 10.1016/0014-5793(93)81759-S
  113. {'key': 'e_1_2_1_114_2', 'first-page': '14205', 'article-title': 'Molecular cloning and expression of a cDNA encoding a novel isoenzyme of protein kinase C (nPKC). A new member of the nPKC family expressed in skeletal muscle, megakaryoblastic cells, and platelets [published erratum appears in J Biol Chem 1994;269:31322]', 'volume': '268', 'author': 'Chang JD', 'year': '1993', 'journal-title': 'J Biol Chem'} / J Biol Chem / Molecular cloning and expression of a cDNA encoding a novel isoenzyme of protein kinase C (nPKC). A new member of the nPKC family expressed in skeletal muscle, megakaryoblastic cells, and platelets [published erratum appears in J Biol Chem 1994;269:31322] by Chang JD (1993)
  114. 10.4049/jimmunol.160.5.2207 / J Immunol / Different protein kinase C isoenzymes regulate IL‐2receptor expression or IL‐2synthesis in human lymphocytes stimulated via the TCR by Szamel M (1998)
  115. 10.1128/MCB.16.4.1842
  116. 10.1093/emboj/17.11.3101
  117. {'key': 'e_1_2_1_118_2', 'first-page': '839', 'article-title': 'Vav and Slp‐76interact and functionally cooperate in 11‐2gene activation', 'volume': '184', 'author': 'Wu J', 'year': '1996', 'journal-title': 'J Exp Med'} / J Exp Med / Vav and Slp‐76interact and functionally cooperate in 11‐2gene activation by Wu J (1996)
  118. 10.1016/S1074-7613(00)80456-2
  119. 10.1146/annurev.immunol.14.1.259
  120. 10.1074/jbc.273.11.6013
  121. 10.1038/385083a0
  122. 10.1016/1074-7613(94)90008-6
  123. 10.1126/science.1621102
  124. 10.1126/science.273.5274.503
  125. {'key': 'e_1_2_1_126_2', 'first-page': 'WP270', 'article-title': 'Cells deficient in the type‐1 inositol 1,4,5‐trisphosphate receptor are resistant to apoptosis', 'volume': '72', 'author': 'Jayaraman T', 'year': '1997', 'journal-title': 'Biophys J'} / Biophys J / Cells deficient in the type‐1 inositol 1,4,5‐trisphosphate receptor are resistant to apoptosis by Jayaraman T (1997)
  126. 10.4049/jimmunol.143.6.1801 / J Immunol / Calcium‐dependent killing of immature thymocytes by stimulation via the CD3/T cell receptor complex by McConkey DJ (1989)
  127. 10.1089/jir.1989.9.633
  128. 10.1016/S0092-8674(88)91307-4
  129. 10.1038/337270a0
  130. 10.1016/0092-8674(89)90107-4
  131. 10.1128/MCB.11.6.3052
  132. 10.1084/jem.180.3.977
  133. 10.1126/science.7510419
  134. 10.1016/S1074-7613(00)80262-9
  135. 10.1016/S0092-8674(05)80086-8 / Cell / Targeted disruption of IRE‐1 or IRE‐2 results in abnormal type I IFN gene induction and aberrant lymphocyte development by Matsuyama T (1993)
  136. 10.1002/j.1460-2075.1994.tb06805.x
  137. 10.1016/S1074-7613(00)80527-0
  138. 10.1126/science.8102208
  139. 10.1016/0092-8674(93)90226-G
  140. 10.1016/0092-8674(93)90225-F
  141. 10.1111/j.1600-065X.1993.tb00646.x
  142. 10.4049/jimmunol.158.7.3205 / J Immunol / Alterations in the level of CD45surface expression affect the outcome of thymic selection by Wallace VA (1997)
  143. 10.4049/jimmunol.154.8.3636 / J Immunol / Intacellular signaling events during positive and negative selection of CD4+CD8+ thymocytes in vitro by Anderson G (1995)
  144. 10.1084/jem.179.6.2027
  145. 10.1146/annurev.immunol.14.1.73
  146. 10.1016/S0092-8674(05)80068-6
  147. 10.1016/1074-7613(94)90043-4
  148. 10.1126/science.8202713
  149. 10.1126/science.8202712
  150. 10.1016/0092-8674(94)90368-9
  151. 10.1002/eji.1830260229
  152. 10.1016/0092-8674(94)90132-5
  153. 10.1126/science.8438157
  154. 10.1073/pnas.88.2.532
  155. 10.1038/382816a0
  156. {'issue': '3', 'key': 'e_1_2_1_157_2', 'first-page': '439', 'article-title': 'DNA damage‐induced apoptosis and Ice gene induction in mitogenically activated T lymphocytes require IRF‐1', 'volume': '11', 'author': 'Tamura T', 'year': '1997', 'journal-title': 'Leukemia'} / Leukemia / DNA damage‐induced apoptosis and Ice gene induction in mitogenically activated T lymphocytes require IRF‐1 by Tamura T (1997)
  157. 10.1038/376596a0
  158. 10.1146/annurev.immunol.15.1.235
  159. 10.1046/j.1365-2443.1996.08008.x
  160. 10.1016/S0065-2776(08)60877-9
  161. 10.1159/000163917
  162. 10.1006/clin.1993.1116
  163. 10.1111/j.1699-0463.1997.tb00532.x
  164. 10.1146/annurev.iy.12.040194.000245
  165. 10.1111/j.1749-6632.1988.tb21632.x
  166. 10.1016/S0092-8674(94)90562-2
  167. 10.1016/0092-8674(95)90161-2
  168. 10.1038/334395a0
  169. 10.1016/0092-8674(88)90425-4
  170. 10.1111/j.1600-065X.1986.tb01474.x
  171. 10.1126/science.3107126
  172. 10.1002/j.1460-2075.1988.tb02871.x
  173. 10.1016/0167-5699(92)90044-8
  174. 10.1093/intimm/6.6.881
  175. 10.1073/pnas.93.5.2169
  176. 10.1016/0092-8674(92)90453-J
  177. 10.1073/pnas.89.20.9529
  178. 10.1084/jem.178.5.1807
  179. 10.1073/pnas.92.2.354
  180. 10.1111/j.1749-6632.1995.tb44482.x
  181. 10.1084/jem.182.4.953
  182. 10.1016/1074-7613(95)90174-4
  183. 10.1016/0092-8674(81)90421-9
  184. 10.1084/jem.181.3.1245
  185. 10.1126/science.1831564
  186. 10.4049/jimmunol.153.12.5491 / J immunol / TCR selection and allelic exclusion in RAG transgenic mice that exhibit abnormal T cell localization in lymph nodes and lymphatics by Wayne J (1994)
  187. 10.1093/intimm/3.1.75
  188. 10.4049/jimmunol.161.4.1718 / J Immnnol / Receptor specific allelic exclusion of TCRVα chains during development by Boyd R (1998)
  189. 10.4049/jimmunol.160.8.3883 / J Immunol / Post‐translational regulation of TCR V alpha allelic exclusion during T cell differentiation by Alam SM (1998)
  190. 10.4049/jimmunol.161.2.585 / J immunol / TCR transgenic mice in which usage of transgenic α‐and β‐chains is highly dependent on the level of selectuig ligand by Kersb GJ (1998)
  191. 10.1126/science.272.5270.1935
  192. 10.1074/jbc.271.37.22310
  193. 10.1002/bies.950181107
  194. 10.1002/eji.1830260516
  195. 10.1016/0092-8674(92)90208-T
  196. 10.1084/jem.178.5.1701
  197. 10.1038/346861a0
  198. 10.1126/science.273.5277.963
  199. 10.1002/eji.1830270621
  200. 10.1016/S1074-7613(00)80500-2
  201. 10.1038/384134a0
  202. 10.1126/science.274.5285.209 / Science / An αγ T cell receptor structure at 2.5A and its orientation in the TCR‐MHC complex by Garcia KC (1996)
  203. 10.1126/science.279.5354.1166
  204. 10.1038/372100a0
  205. {'key': 'e_1_2_1_206_2', 'first-page': '148', 'article-title': 'Serial triggering of many T‐cell receptors by a few peptidc‐MHC complexes', 'volume': '378', 'author': 'Vahtutd S', 'year': '1995', 'journal-title': 'Nature'} / Nature / Serial triggering of many T‐cell receptors by a few peptidc‐MHC complexes by Vahtutd S (1995)
  206. 10.4049/jimmunol.139.2.625 / J Immunol / Cell surface T3expression requires the presence of both α‐and β‐chains of die T cell receptor by Saito T (1987)
  207. 10.1126/science.8211163
  208. 10.1126/science.276.5321.2057
  209. 10.1126/science.277.5334.1950
  210. 10.1084/jem.186.8.1269
  211. 10.1093/intimm/6.11.1661
  212. 10.1007/BF00191226
  213. 10.1126/science.275.5298.356
Dates
Type When
Created 19 years, 3 months ago (April 30, 2006, 12:56 a.m.)
Deposited 1 year, 9 months ago (Oct. 28, 2023, 2:57 a.m.)
Indexed 1 year, 9 months ago (Oct. 29, 2023, 1 a.m.)
Issued 26 years, 10 months ago (Oct. 1, 1998)
Published 26 years, 10 months ago (Oct. 1, 1998)
Published Online 19 years, 3 months ago (April 28, 2006)
Published Print 26 years, 10 months ago (Oct. 1, 1998)
Funders 0

None

@article{Penninger_1998, title={Thymocyte selection in Vav and IRF‐1 gene‐deficient mice}, volume={165}, ISSN={1600-065X}, url={http://dx.doi.org/10.1111/j.1600-065x.1998.tb01237.x}, DOI={10.1111/j.1600-065x.1998.tb01237.x}, number={1}, journal={Immunological Reviews}, publisher={Wiley}, author={Penninger, Josef M. and Mak, Tak W.}, year={1998}, month=oct, pages={149–166} }