Essential role of TGF‐β in the natural resistance to experimental allergic encephalomyelitis in rats

• Published in: European journal of immunology 2001-04, Vol.31 (4), p.1132-1140
• Main Authors: Cautain, Bastien, Damoiseaux, Jan, Bernard, Isabelle, van Straaten, Henny, van Breda Vriesman, Peter, Boneu, Bernard, Druet, Philippe, Saoudi, Abdelhadi
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Monoclonal - immunology; Autoimmune; Blood Platelets - physiology; CD8-Positive T-Lymphocytes - immunology; Cell Division; Cytokine; Disease Susceptibility - immunology; Encephalomyelitis, Autoimmune, Experimental - immunology; Experimental allergic encephalomyelitis; Female; Flow Cytometry; g-Interferon; Interferon-gamma - immunology; Interleukin-10 - immunology; Interleukin-4 - antagonists & inhibitors; Interleukin-4 - genetics; Interleukin-4 - immunology; Leukocyte Common Antigens - immunology; Lymph Nodes - immunology; myelin basic protein; Myelin Basic Protein - immunology; Neutralization Tests; Rats; Rats, Inbred BN; Rats, Inbred Lew; RNA, Messenger - genetics; RNA, Messenger - metabolism; Rodent; Suppression; Th1 Cells - immunology; Transforming Growth Factor beta - antagonists & inhibitors; Transforming Growth Factor beta - biosynthesis; Transforming Growth Factor beta - immunology; Transforming Growth Factor beta1; transforming growth factor-^b
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/1521-4141(200104)31:4<1132::AID-IMMU1132>3.0.CO;2-N

Experimental allergic encephalomyelitis (EAE) is a T cell‐mediated autoimmune disease induced in susceptible rat strains by a single immunization with myelin basic protein (MBP). The Lewis (LEW) strain is susceptible to disease induction while the Brown Norway (BN) strain is resistant. This resistance involves non‐MHC genes since congenic BN‐1L rats, with LEW MHC on a BN‐derived background, are also resistant. In the present study we show that, upon immunization with MBP, the non‐MHC‐encoded resistance to develop clinical EAE in BN‐1L rats is associated with a decreased production of IFN‐γ. This may be due to a difference between LEW and BN‐1L rats in their ability to produce regulatory cytokines such as IL‐4, IL‐10 and TGF‐β. In comparison to LEW rats, immune lymph node cells from BN‐1L rats express an increased amount of IL‐4 mRNA but produce less IL‐10. Furthermore, the sera from BN‐1L rats contain higher amounts of active TGF‐β1. Therefore, we have investigated the involvement of IL‐4 and TGF‐β in the resistance of BN‐1L rats to develop EAE using neutralizing mAb. Neutralization of TGF‐β, but not IL‐4, renders BN‐1L rats susceptible to clinical EAEwithout affecting the proliferation or the cytokine repertoire of immune lymph node cells. With respect to the origin of the endogenous TGF‐β production, we excluded the involvement of CD8 T cells and discuss a possible role of platelets and of CD4 T cells exhibiting the CD45RClow phenotype.