CD28-B7 costimulatory blockade by CTLA4Ig prevents actively induced experimental autoimmune encephalomyelitis and inhibits Th1 but spares Th2 cytokines in the central nervous system

S. J. Khoury, Enver Akalin, A. Chandraker, L. A. Turka, P. S. Linsley, M. H. Sayegh, W. W. Hancock

Research output: Contribution to journalArticle

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Abstract

We studied the contribution of the CD28-B7 costimulatory T cell activation pathway to the pathogenesis of experimental autoimmune encephalomyelitis in the Lewis rat model. Systemic administration of CTLA4Ig suppressed clinical disease and was effective even when CTLA4Ig was delayed until day 10 postimmunization, a time when pathologic disease is evident. This protection was not reversible by systemic administration of high doses of IL-2. Detailed immunohistologic studies showed that CTLA4Ig therapy resulted in suppression of the inflammatory response with inhibition of Th1 (IL-2 and IFN-γ) and sparing of Th2 (IL-4, IL-10, and IL-13) cytokines in the central nervous system. These results indicate that the CD28-B7 T cell costimulatory pathway plays an important role in experimental autoimmune encephalomyelitis, a Th1- mediated disease, and suggest that blockade of this costimulatory pathway protects against active disease by causing a state of immune deviation towards Th2 function. The ability of CTLA4Ig to treat animals with pathologically established disease may have important clinical implications for patients with multiple sclerosis.

Original languageEnglish (US)
Pages (from-to)4521-4524
Number of pages4
JournalJournal of Immunology
Volume155
Issue number10
StatePublished - 1995
Externally publishedYes

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Autoimmune Experimental Encephalomyelitis
Central Nervous System
Cytokines
Interleukin-2
T-Lymphocytes
Interleukin-13
Interleukin-4
Interleukin-10
Multiple Sclerosis

ASJC Scopus subject areas

  • Immunology

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CD28-B7 costimulatory blockade by CTLA4Ig prevents actively induced experimental autoimmune encephalomyelitis and inhibits Th1 but spares Th2 cytokines in the central nervous system. / Khoury, S. J.; Akalin, Enver; Chandraker, A.; Turka, L. A.; Linsley, P. S.; Sayegh, M. H.; Hancock, W. W.

In: Journal of Immunology, Vol. 155, No. 10, 1995, p. 4521-4524.

Research output: Contribution to journalArticle

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abstract = "We studied the contribution of the CD28-B7 costimulatory T cell activation pathway to the pathogenesis of experimental autoimmune encephalomyelitis in the Lewis rat model. Systemic administration of CTLA4Ig suppressed clinical disease and was effective even when CTLA4Ig was delayed until day 10 postimmunization, a time when pathologic disease is evident. This protection was not reversible by systemic administration of high doses of IL-2. Detailed immunohistologic studies showed that CTLA4Ig therapy resulted in suppression of the inflammatory response with inhibition of Th1 (IL-2 and IFN-γ) and sparing of Th2 (IL-4, IL-10, and IL-13) cytokines in the central nervous system. These results indicate that the CD28-B7 T cell costimulatory pathway plays an important role in experimental autoimmune encephalomyelitis, a Th1- mediated disease, and suggest that blockade of this costimulatory pathway protects against active disease by causing a state of immune deviation towards Th2 function. The ability of CTLA4Ig to treat animals with pathologically established disease may have important clinical implications for patients with multiple sclerosis.",
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AU - Chandraker, A.

AU - Turka, L. A.

AU - Linsley, P. S.

AU - Sayegh, M. H.

AU - Hancock, W. W.

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