Antagonizing the alpha 4 beta 1 Integrin, but Not alpha 4 beta 7, Inhibits Leukocytic Infiltration of the Central Nervous System in Rhesus Monkey Experimental Autoimmune Encephalomyelitis

• Published in: The Journal of immunology (1950) Vol. 190; no. 5; pp. 1961 - 1973
• Main Authors: Haanstra, Krista G, Hofman, Sam O, Lopes Estevao, Dave M, Blezer, Erwin LA, Bauer, Jan, Yang, Li-Li, Wyant, Tim, Csizmadia, Vilmos, 't Hart, Bert A, Fedyk, Eric R
• Format: Journal Article
• Language: English
• Published: 01.03.2013
• Subjects: Macaca mulatta; Primates
• ISSN: 0022-1767
• DOI: 10.4049/jimmunol.1202490

The immune system is characterized by the preferential migration of lymphocytes through specific tissues (i.e., tissue tropism). Tissue tropism is mediated, in part, by the alpha 4 integrins expressed by T lymphocytes. The alpha 4 beta 1 integrin mediates migration of memory T lymphocytes into the CNS, whereas the alpha 4 beta 7 integrin mediates migration preferentially into gastrointestinal tissue. This paradigm was established primarily from investigations in rodents; thus, the objective of this investigation was to determine if blocking the alpha 4 beta 7 integrin exclusively would affect migration of T lymphocytes into the CNS of primates. The effects of the dual alpha 4 beta 1 and alpha 4 beta 7 antagonist natalizumab were compared with those of the alpha 4 beta 7 antagonist vedolizumab on experimental autoimmune encephalomyelitis in the rhesus monkey. Animals received an initial i.v. bolus of placebo, natalizumab (30 mg/kg), or vedolizumab (30 mg/kg) before intracutaneous immunization with recombinant human myelin oligodendrocyte glycoprotein and then Ab once weekly thereafter. Natalizumab prevented CNS inflammation and demyelination significantly (p < 0.05), compared with time-matched placebo control animals, whereas vedolizumab did not inhibit these effects, despite saturating the alpha 4 beta 7 integrin in each animal for the duration of the investigation. These results demonstrate that blocking alpha 4 beta 7 exclusively does not inhibit immune surveillance of the CNS in primates.