Soluble antigen therapy induces apoptosis of autoreactive T cells preferentially in the target organ rather than in the peripheral lymphoid organs

Ishigami, Tsuyoshi, White, Catherine A. and Pender, Michael P. (1998) Soluble antigen therapy induces apoptosis of autoreactive T cells preferentially in the target organ rather than in the peripheral lymphoid organs. European Journal of Immunology, 28 5: 1626-1635. doi:10.1002/(SICI)1521-4141(199805)28:05<1626::AID-IMMU1626>3.0.CO;2-B


Author Ishigami, Tsuyoshi
White, Catherine A.
Pender, Michael P.
Title Soluble antigen therapy induces apoptosis of autoreactive T cells preferentially in the target organ rather than in the peripheral lymphoid organs
Journal name European Journal of Immunology   Check publisher's open access policy
ISSN 0014-2980
1521-4141
Publication date 1998-05
Sub-type Article (original research)
DOI 10.1002/(SICI)1521-4141(199805)28:05<1626::AID-IMMU1626>3.0.CO;2-B
Volume 28
Issue 5
Start page 1626
End page 1635
Total pages 10
Place of publication Weinheim, Germany
Publisher Wiley - V C H Verlag
Language eng
Formatted abstract
The administration of soluble myelin proteins is an effective way of down-regulating the inflammation in the central nervous system (CNS) in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. To shed more light on the mechanism of this antigen-specific therapy, we determined the effect of the intraperitoneal (i.p.) injection of soluble myelin basic protein (MBP) on T cell apoptosis in the CNS and peripheral lymphoid organs of Lewis rats with EAE induced by inoculation with MBP and complete Freund's adjuvant. In particular we assessed the level of apoptosis of Vβ8.2+ T cells, which constitute the predominant encephalitogenic MBP-reactive T cell population in the Lewis rat. The daily i.p. injection of MBP for 3 days from the onset of neurological signs inhibited the further development of neurological signs of EAE. Using two-color flow cytometry we found that a single i.p. injection of MBP increased the level of apoptosis of the Vβ8.2+ T cell population in the CNS to 26.2% compared to 7.4% in saline-treated rats and 7.6% in ovalbumin-treated rats. In contrast, treatment with MBP did not increase the level of apoptosis of the Vβ8.2+ population in the popliteal lymph node draining the inoculation site (1.4%) or in the spleen (1.6%) above that occurring in saline-treated rats (1.6% and 1.1%, respectively). Limiting dilution analysis revealed that the frequency of T cells reactive to the major encephalitogenic epitope, MBP72-89 was decreased in the CNS but not in the popliteal lymph node by this treatment. Three-color flow cytometry in MBP-treated rats demonstrated that CNS Vβ38.2+ T cells expressing Fas (CD95) and Fas ligand were highly vulnerable to apoptosis compared to Vβ8.2+ T cells not expressing these proteins. We conclude that the i.p. injection of MBP increases the spontaneously occurring Fas-mediated activation-induced apoptosis of auto-reactive T cells in the CNS in EAE and that this contributes to the therapeutic effect of the injection.
Keyword Apoptosis
T cell
Experimental autoimmune encephalomyelitis
Fas (CD95)
Treatment
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ
Additional Notes Article first published online: 14 Decemebr 1998.

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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