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Pender MP. CD8+ T-Cell Deficiency, Epstein-Barr Virus Infection, Vitamin D Deficiency, and Steps to Autoimmunity: A Unifying Hypothesis. Autoimmune Dis. 2012;2012:189096doi: 10.1155/2012/189096.
Pender, M. P. (2012). CD8+ T-Cell Deficiency, Epstein-Barr Virus Infection, Vitamin D Deficiency, and Steps to Autoimmunity: A Unifying Hypothesis. Autoimmune diseases, 2012189096. https://doi.org/10.1155/2012/189096
Pender, Michael P. "CD8+ T-Cell Deficiency, Epstein-Barr Virus Infection, Vitamin D Deficiency, and Steps to Autoimmunity: A Unifying Hypothesis." Autoimmune diseases vol. 2012 (2012): 189096. doi: https://doi.org/10.1155/2012/189096
Pender MP. CD8+ T-Cell Deficiency, Epstein-Barr Virus Infection, Vitamin D Deficiency, and Steps to Autoimmunity: A Unifying Hypothesis. Autoimmune Dis. 2012;2012:189096. doi: 10.1155/2012/189096. Epub 2012 Jan 24. PMID: 22312480; PMCID: PMC3270541.
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Autoimmune Dis. 2012;2012:189096. doi: 10.1155/2012/189096. Epub 2012 Jan 24.

CD8+ T-Cell Deficiency, Epstein-Barr Virus Infection, Vitamin D Deficiency, and Steps to Autoimmunity: A Unifying Hypothesis.

Autoimmune diseases

Michael P Pender

Affiliations

  1. School of Medicine, The University of Queensland, Brisbane, QLD 4072, Australia.

PMID: 22312480 PMCID: PMC3270541 DOI: 10.1155/2012/189096

Abstract

CD8+ T-cell deficiency is a feature of many chronic autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, Sjögren's syndrome, systemic sclerosis, dermatomyositis, primary biliary cirrhosis, primary sclerosing cholangitis, ulcerative colitis, Crohn's disease, psoriasis, vitiligo, bullous pemphigoid, alopecia areata, idiopathic dilated cardiomyopathy, type 1 diabetes mellitus, Graves' disease, Hashimoto's thyroiditis, myasthenia gravis, IgA nephropathy, membranous nephropathy, and pernicious anaemia. It also occurs in healthy blood relatives of patients with autoimmune diseases, suggesting it is genetically determined. Here it is proposed that this CD8+ T-cell deficiency underlies the development of chronic autoimmune diseases by impairing CD8+ T-cell control of Epstein-Barr virus (EBV) infection, with the result that EBV-infected autoreactive B cells accumulate in the target organ where they produce pathogenic autoantibodies and provide costimulatory survival signals to autoreactive T cells which would otherwise die in the target organ by activation-induced apoptosis. Autoimmunity is postulated to evolve in the following steps: (1) CD8+ T-cell deficiency, (2) primary EBV infection, (3) decreased CD8+ T-cell control of EBV, (4) increased EBV load and increased anti-EBV antibodies, (5) EBV infection in the target organ, (6) clonal expansion of EBV-infected autoreactive B cells in the target organ, (7) infiltration of autoreactive T cells into the target organ, and (8) development of ectopic lymphoid follicles in the target organ. It is also proposed that deprivation of sunlight and vitamin D at higher latitudes facilitates the development of autoimmune diseases by aggravating the CD8+ T-cell deficiency and thereby further impairing control of EBV. The hypothesis makes predictions which can be tested, including the prevention and successful treatment of chronic autoimmune diseases by controlling EBV infection.

References

  1. Clin Diagn Lab Immunol. 1995 Mar;2(2):205-8 - PubMed
  2. Acta Derm Venereol. 1983;63(5):422-4 - PubMed
  3. J Immunol. 2004 Jan 15;172(2):1287-94 - PubMed
  4. J Virol. 1984 Nov;52(2):722-5 - PubMed
  5. Acta Derm Venereol. 1982;62(3):201-4 - PubMed
  6. Am J Pathol. 2000 Jul;157(1):51-7 - PubMed
  7. Aust N Z J Surg. 1984 Jun;54(3):265-9 - PubMed
  8. J Clin Invest. 1998 Nov 15;102(10):1831-40 - PubMed
  9. Am J Pathol. 1993 Jul;143(1):49-64 - PubMed
  10. Ir J Med Sci. 1985 Nov;154(11):416-21 - PubMed
  11. J Rheumatol. 1995 Nov;22(11):2092-9 - PubMed
  12. Neurology. 2004 Jun 22;62(12):2277-82 - PubMed
  13. J Clin Invest. 2002 May;109(9):1231-40 - PubMed
  14. J Immunol. 2007 Jan 1;178(1):547-56 - PubMed
  15. J Reprod Immunol. 1991 May;20(1):85-91 - PubMed
  16. J Exp Med. 2008 Aug 4;205(8):1763-73 - PubMed
  17. J Clin Invest. 1998 Sep 1;102(5):1045-50 - PubMed
  18. J Epidemiol Community Health. 1998 Feb;52(2):101-4 - PubMed
  19. J Neurol Sci. 1983 Dec;62(1-3):219-32 - PubMed
  20. Cytometry B Clin Cytom. 2003 Mar;52(1):32-6 - PubMed
  21. J Clin Invest. 1998 Sep 1;102(5):938-46 - PubMed
  22. JAMA. 2005 May 25;293(20):2496-500 - PubMed
  23. J Clin Endocrinol Metab. 2008 Mar;93(3):729-34 - PubMed
  24. Autoimmun Rev. 2011 Dec;11(2):88-97 - PubMed
  25. J Neuroimmunol. 2002 Apr;125(1-2):185-97 - PubMed
  26. Acta Med Croatica. 1993;47(3):113-8 - PubMed
  27. Am J Kidney Dis. 1998 Nov;32(5):785-93 - PubMed
  28. N Engl J Med. 1980 Jul 17;303(3):125-9 - PubMed
  29. Trends Immunol. 2003 Nov;24(11):584-8 - PubMed
  30. Hepatology. 2008 Dec;48(6):1906-12 - PubMed
  31. Lancet. 1983 Mar 12;1(8324):545-8 - PubMed
  32. J Clin Invest. 1984 Jun;73(6):1789-95 - PubMed
  33. Rheumatol Int. 1982;2(4):155-9 - PubMed
  34. Am J Pathol. 2007 Feb;170(2):457-68 - PubMed
  35. World J Gastroenterol. 2006 Jun 21;12(23):3628-35 - PubMed
  36. Proc Eur Dial Transplant Assoc. 1983;19:635-41 - PubMed
  37. Tissue Antigens. 2011 Feb;77(2):107-11 - PubMed
  38. Ann Allergy. 1990 Aug;65(2):143-5 - PubMed
  39. Photodermatol Photoimmunol Photomed. 1997 Aug;13(4):139-42 - PubMed
  40. Clin Diagn Lab Immunol. 2003 May;10(3):443-5 - PubMed
  41. Eur Neurol. 1992;32(4):190-4 - PubMed
  42. Clin Exp Immunol. 1992 Mar;87(3):444-9 - PubMed
  43. Blood. 2008 Feb 1;111(3):1448-55 - PubMed
  44. Environ Health Perspect. 2010 Jul;118(7):957-61 - PubMed
  45. J Immunol. 1982 Jan;128(1):351-4 - PubMed
  46. Arthritis Rheum. 1994 Oct;37(10):1441-4 - PubMed
  47. JAMA. 2001 Dec 26;286(24):3083-8 - PubMed
  48. J Immunol. 1999 Nov 15;163(10):5735-40 - PubMed
  49. Neurology. 2000 Jul 25;55(2):178-84 - PubMed
  50. J Exp Med. 2007 Nov 26;204(12):2899-912 - PubMed
  51. Int J Immunopharmacol. 1981;3(3):313-9 - PubMed
  52. Science. 1985 Apr 5;228(4695):85-9 - PubMed
  53. Arthritis Rheum. 2003 Nov;48(11):3187-201 - PubMed
  54. Gastroenterol Jpn. 1992 Dec;27(6):751-8 - PubMed
  55. J Infect Dis. 2007 Dec 15;196(12):1749-53 - PubMed
  56. Clin Immunol Immunopathol. 1982 Feb;22(2):270-8 - PubMed
  57. J Clin Virol. 2011 Jan;50(1):31-6 - PubMed
  58. J Exp Med. 2009 Jun 8;206(6):1423-34 - PubMed
  59. Rev Med Virol. 2006 Sep-Oct;16(5):297-310 - PubMed
  60. J Neurol Neurosurg Psychiatry. 2012 Mar;83(3):353-4 - PubMed
  61. Brain. 2007 Apr;130(Pt 4):1089-104 - PubMed
  62. Am J Cardiol. 1985 Mar 1;55(6):755-8 - PubMed
  63. Brain Pathol. 2004 Apr;14(2):164-74 - PubMed
  64. Ann Rheum Dis. 2007 Jun;66(6):720-6 - PubMed
  65. J Pathol. 1996 Mar;178(3):323-9 - PubMed
  66. Proc Natl Acad Sci U S A. 2005 Dec 13;102(50):18093-8 - PubMed
  67. Lancet. 1998 Mar 28;351(9107):978-81 - PubMed
  68. Cancer Lett. 2006 Feb 8;232(2):189-98 - PubMed
  69. Autoimmun Rev. 2011 Jun;10(8):490-4 - PubMed
  70. Blood. 2011 May 12;117(19):5123-32 - PubMed
  71. Arthritis Rheum. 2001 May;44(5):1122-6 - PubMed
  72. J Clin Immunol. 1989 Mar;9(2):103-10 - PubMed
  73. Am J Pathol. 2001 Sep;159(3):861-73 - PubMed
  74. J Neurol Sci. 1990 Jul;97(2-3):163-71 - PubMed
  75. Nat Rev Rheumatol. 2011 May;7(5):263-71 - PubMed
  76. J Clin Invest. 1980 Nov;66(5):1171-4 - PubMed
  77. Vet Immunol Immunopathol. 1993 Sep;38(1-2):75-89 - PubMed
  78. Clin Immunol. 2009 Jul;132(1):19-31 - PubMed
  79. J Pediatr. 1999 Oct;135(4):531 - PubMed
  80. Lancet. 1980 Dec 6;2(8206):1221-3 - PubMed
  81. Arthritis Rheum. 2003 May;48(5):1223-8 - PubMed
  82. Science. 2003 Sep 5;301(5638):1374-7 - PubMed
  83. Clin Immunol. 2005 Aug;116(2):192-7 - PubMed
  84. J Infect Dis. 2008 Sep 1;198(5):673-82 - PubMed
  85. Scand J Immunol. 1974;3(3):295-301 - PubMed
  86. Clin Exp Immunol. 1983 Jun;52(3):629-34 - PubMed
  87. Dig Dis Sci. 1987 Jul;32(7):720-5 - PubMed
  88. Viral Immunol. 2011 Apr;24(2):143-9 - PubMed
  89. Nephron. 1990;54(2):185-6 - PubMed
  90. Genes Immun. 2000 Oct;1(7):423-7 - PubMed
  91. Wien Med Wochenschr. 2009;159(13-14):337-41 - PubMed
  92. Ophthalmology. 1990 Aug;97(8):976-84 - PubMed
  93. Neurology. 2006 Dec 12;67(11):2063-5 - PubMed
  94. J Clin Immunol. 1985 Jul;5(4):254-60 - PubMed
  95. J Immunol. 2005 Jun 1;174(11):6599-607 - PubMed
  96. Autoimmunity. 2006 Feb;39(1):63-70 - PubMed
  97. J Exp Med. 1999 Aug 16;190(4):567-76 - PubMed
  98. Ann Neurol. 2010 Jun;67(6):726-38 - PubMed
  99. Autoimmun Rev. 2012 Jan;11(3):163-6 - PubMed
  100. Am J Pathol. 1996 Nov;149(5):1511-7 - PubMed
  101. J Immunol. 1983 Jul;131(1):171-4 - PubMed
  102. Arthritis Rheum. 1988 Aug;31(8):1014-21 - PubMed
  103. Eur J Immunol. 1995 Oct;25(10):2775-82 - PubMed
  104. Dis Nerv Syst. 1948 Nov;9(11):342-6 - PubMed
  105. Clin Exp Rheumatol. 1995 Nov-Dec;13(6):745-8 - PubMed
  106. Ann Neurol. 2010 Jun;67(6):824-30 - PubMed
  107. Endocrine. 2008 Apr;33(2):171-5 - PubMed
  108. Arch Biochem Biophys. 2000 Feb 15;374(2):334-8 - PubMed
  109. J Virol. 2005 Jan;79(2):1296-307 - PubMed
  110. J Neurol Neurosurg Psychiatry. 1986 Aug;49(8):905-12 - PubMed
  111. J Neurol Neurosurg Psychiatry. 2009 May;80(5):498-505 - PubMed
  112. Am J Respir Crit Care Med. 1999 Apr;159(4 Pt 1):1336-41 - PubMed
  113. Blood. 2006 Nov 1;108(9):2942-9 - PubMed
  114. Am J Hum Genet. 2010 Jan;86(1):88-92 - PubMed
  115. Am J Gastroenterol. 1999 Jun;94(6):1582-6 - PubMed
  116. Immunology. 2010 Apr;129(4):474-81 - PubMed
  117. Arthritis Rheum. 1983 Jul;26(7):841-7 - PubMed
  118. Arthritis Rheum. 1982 Apr;25(4):419-26 - PubMed
  119. J Clin Neurosci. 2000 Sep;7(5):434-7 - PubMed
  120. PLoS Pathog. 2009 Jul;5(7):e1000496 - PubMed
  121. J Nephrol. 2005 May-Jun;18(3):328-33 - PubMed
  122. Folia Neuropathol. 2006;44(1):67-71 - PubMed
  123. Ann Neurol. 2007 Apr;61(4):288-99 - PubMed
  124. J Rheumatol. 1986 Apr;13(2):320-6 - PubMed
  125. Life Sci. 1997;61(2):147-52 - PubMed
  126. Arch Neurol. 1980 Feb;37(2):94-6 - PubMed
  127. J Virol. 2009 Apr;83(8):3968-76 - PubMed
  128. Diabetes. 1988 Nov;37(11):1484-8 - PubMed
  129. Autoimmun Rev. 2011 Oct;10(12):733-43 - PubMed
  130. J Clin Invest. 1997 Dec 15;100(12):3019-26 - PubMed
  131. Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):221-5 - PubMed
  132. Scand J Immunol. 1995 May;41(5):481-6 - PubMed
  133. N Engl J Med. 1981 Nov 19;305(21):1238-43 - PubMed
  134. Clin Diagn Lab Immunol. 1995 Mar;2(2):233-5 - PubMed
  135. Annu Rev Immunol. 2007;25:587-617 - PubMed
  136. Scand J Haematol. 1986 Oct;37(4):316-8 - PubMed
  137. N Engl J Med. 2004 Mar 25;350(13):1328-37 - PubMed
  138. Nat Immunol. 2002 Oct;3(10):940-3 - PubMed
  139. Ann Neurol. 1982 Feb;11(2):170-6 - PubMed
  140. Clin Exp Immunol. 2009 Dec;158 Suppl 1:43-50 - PubMed
  141. Diabetologia. 1984 Jun;26(6):426-30 - PubMed
  142. Hum Genet. 1998 Oct;103(4):475-82 - PubMed
  143. Arthritis Rheum. 2009 Apr;60(4):1160-72 - PubMed
  144. J Virol. 2004 May;78(10):5194-204 - PubMed
  145. Liver Int. 2003 Oct;23(5):323-8 - PubMed
  146. Exp Clin Endocrinol Diabetes. 1996;104(1):89-92 - PubMed
  147. Anadolu Kardiyol Derg. 2001 Jun;1(2):98-100 - PubMed
  148. Immunol Lett. 1995 Sep;47(3):209-13 - PubMed
  149. Neurology. 2008 Sep 23;71(13):1033-5 - PubMed
  150. J Mol Diagn. 2008 Jul;10(4):279-92 - PubMed
  151. Acta Neurol Scand. 2004 Apr;109(4):270-5 - PubMed
  152. Clin Immunol. 2004 Oct;113(1):4-13 - PubMed
  153. J Immunol. 1983 Oct;131(4):1797-801 - PubMed
  154. Clin Endocrinol (Oxf). 1981 Sep;15(3):259-63 - PubMed
  155. Hepatogastroenterology. 1994 Jun;41(3):239-43 - PubMed
  156. Clin Exp Immunol. 1990 Feb;79(2):170-4 - PubMed
  157. PLoS One. 2010 Apr 12;5(4):e10126 - PubMed
  158. J Virol. 1987 May;61(5):1416-20 - PubMed
  159. Arch Neurol. 1983 Jul;40(7):406-8 - PubMed
  160. Nat Med. 1995 Dec;1(12):1279-83 - PubMed
  161. Ann Rheum Dis. 2005 Oct;64(10):1485-9 - PubMed
  162. Hum Pathol. 1978 Sep;9(5):495-515 - PubMed
  163. Am J Hum Genet. 1986 Nov;39(5):584-602 - PubMed
  164. JAMA. 2006 Dec 20;296(23):2832-8 - PubMed
  165. BMC Neurol. 2011 Aug 03;11:95 - PubMed
  166. Clin Exp Immunol. 1985 Sep;61(3):548-55 - PubMed
  167. Environ Health Perspect. 2003 Apr;111(4):518-23 - PubMed
  168. Gut. 2002 Sep;51(3):364-71 - PubMed
  169. Arthritis Rheum. 2001 Nov;44(11):2633-41 - PubMed
  170. Clin Diagn Lab Immunol. 2004 Jul;11(4):811-3 - PubMed
  171. Lancet. 1971 Jan 23;1(7691):167-8 - PubMed
  172. Pathol Int. 2000 Apr;50(4):304-12 - PubMed
  173. Ann Intern Med. 1985 Apr;102(4):490-3 - PubMed
  174. Transpl Immunol. 2005 Aug;14(3-4):175-82 - PubMed
  175. Gut. 1984 Jul;25(7):743-7 - PubMed
  176. Proc Natl Acad Sci U S A. 1979 Nov;76(11):5825-8 - PubMed
  177. Blood. 2007 Nov 15;110(10):3715-21 - PubMed
  178. Brain. 2006 Jun;129(Pt 6):1493-506 - PubMed
  179. J Clin Pathol. 1970 Mar;23(2):95-8 - PubMed
  180. Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7415-9 - PubMed
  181. Ann Rheum Dis. 1990 Jan;49(1):40-5 - PubMed
  182. J Immunol. 1994 Sep 15;153(6):2750-7 - PubMed
  183. Eur J Immunol. 1994 Nov;24(11):2609-17 - PubMed
  184. J Neuroimmunol. 1982 Dec;3(4):319-35 - PubMed
  185. J Clin Lab Immunol. 1983 Mar;10(3):127-31 - PubMed
  186. Lancet. 1984 Oct 6;2(8406):768-71 - PubMed
  187. J Exp Med. 1989 Jun 1;169(6):2191-8 - PubMed
  188. Nat Med. 1998 Jun;4(6):713-7 - PubMed
  189. J Infect Dis. 2006 Sep 1;194(5):584-7 - PubMed
  190. Kidney Int. 1981 Aug;20(2):267-74 - PubMed
  191. Brain. 2009 Dec;132(Pt 12):3196-8 - PubMed
  192. Clin Exp Immunol. 1981 Jul;45(1):1-8 - PubMed
  193. Boll Ist Sieroter Milan. 1988;67(4):265-74 - PubMed
  194. Neuroscientist. 2011 Aug;17(4):351-67 - PubMed
  195. Autoimmun Rev. 2009 Jun;8(7):563-8 - PubMed
  196. Clin Exp Immunol. 1983 Apr;52(1):45-53 - PubMed
  197. Int J Mol Med. 2006 May;17(5):911-6 - PubMed
  198. Lancet Neurol. 2007 Sep;6(9):773-81 - PubMed
  199. J Pediatr. 1997 Mar;130(3):388-93 - PubMed
  200. Thorax. 1985 Jun;40(6):405-11 - PubMed
  201. N Engl J Med. 1984 Jul 5;311(1):56 - PubMed
  202. Ann Neurol. 2006 Mar;59(3):499-503 - PubMed
  203. J Clin Endocrinol Metab. 1983 Feb;56(2):251-4 - PubMed
  204. Arthritis Rheum. 1984 Jan;27(1):32-9 - PubMed
  205. Lancet Neurol. 2006 Nov;5(11):924-31 - PubMed

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