Regulation of experimental autoimmune encephalomyelitis by CD4+, CD25+ and CD8+ T cells: Analysis using depleting antibodies

Enrique Montero, Gabriel Nussbaum, Joel F. Kaye, Rolando Perez, Agustin Lage, Avraham Ben-Nun, Irun R. Cohen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

92 Scopus citations

Abstract

Experimental Autoimmune Encephalomyelitis (EAE) can be induced in mice of the C57BL/6 strain by subcutaneous immunization with myelin/oligodendrocyte glycoprotein (MOG) peptide p35-55 in CFA, administered twice at an interval of one week and supplemented with Bordetella pertussis toxin given IV. Here, we studied the effect on the induction of EAE of depleting antibodies to CD4, CD8, or CD25 administered before either the first or the second dose of MOG p35-55. We found that anti-CD4 abolished EAE when given before the first immunization; anti-CD4 did not affect the disease when it was given before the second immunization. Anti-CD8 enhanced EAE induction when given before either of the two immunizations. Anti-CD25 enhanced EAE to the same degree as anti-CD8 when given before the first immunization, but anti-CD25 was even more effective in enhancing EAE when given before the second immunization. The anti-CD25 treatment led to significantly enhanced IFNγ production by T cells responding to MOG p35-55 and persisting anti-MOG antibodies detectable 56 days after the first immunization. Administration of anti-CD8 or anti-CD25 abolished the need for pertussis toxin to induce EAE. These findings are compatible with the idea that CD4 T cells are required for the initial induction of EAE and that the disease is down-regulated by T cells expressing CD8 or CD25. These regulatory T cells exist prior to MOG immunization, but the CD25+ regulators appear to be further amplified by immunization.

Original languageAmerican English
Pages (from-to)1-7
Number of pages7
JournalJournal of Autoimmunity
Volume23
Issue number1
DOIs
StatePublished - Aug 2004
Externally publishedYes

Bibliographical note

Funding Information:
I.R.C. is the incumbent of the Mauerberger Chair of Immunology and the Director of the Center for the Study of Emerging Diseases, Jerusalem. G.N. was supported by a Juvenile Diabetes Research Foundation post-doctoral fellowship.

Keywords

  • CD25
  • CD8
  • CFA
  • EAE
  • IV
  • Immunoregulation
  • MOG
  • PPD
  • complete Freund's adjuvant
  • experimental autoimmune encephalomyelitis
  • intravenously
  • mAb
  • monoclonal antibody
  • mycobacterium-derived purified protein derivative
  • myelin/oligodendrocyte glycoprotein

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