Differential Expression of Cytokines (IL‐2, IFN‐γ, IL‐10) and Adhesion Molecules (VCAM‐1, LFA‐1, CD44) Between Spleen and Lymph Nodes Associates with Remission in Chronic Relapsing Experimental Autoimmune Encephalomyelitis

Abstract

We have recently established chronic relapsing experimental autoimmune encephalomyelitis (CR‐EAE) in SJL mice with a modified protocol. In this model, splenectomy aborts the relapsing–remitting course of the disease, and adoptive transfer of lymphocytes of the local draining lymph nodes (LNs) to naive recipients exacerbates the disease. Adoptive transfer of splenic cells converted acute EAE into CR‐EAE in the naive recipients. In light of the different roles of the spleen and LNs in the evolution of CR‐EAE, we examined by semiquantitative reverse‐transcription polymerase chain reaction (RT‐PCR) whether a differential mRNA expression profile of cytokines and cellular adhesion molecules (CAMs) in spleen versus LN was associated with relapse or remission in CR‐EAE. All the cytokines tested (interleukin‐1β (IL‐1β), IL‐2, IL‐4, IL‐7, IL‐10, interferon‐γ (IFN‐γ)) as well as CAMs (ICAM‐1, ICAM‐2, VCAM‐1, LFA‐1 and CD44) were expressed at substantial levels in both spleen and LNs. Interestingly, disease remission was found to be associated with an increased mRNA expression of IL‐2 and IFN‐γ in LNs and a decreased IL‐10 mRNA level in the spleen. On the other hand, an increased mRNA expression of VCAM‐1, LFA‐1 and CD44 was observed in the spleens in comparison with that in LNs of mice, with remission. During relapses, mRNA expression of the tested molecules did not significantly differ between spleens and LNs. Our results suggest that a differential and polarized expression profile of certain cytokines and CAMs in spleen versus LN could provide molecular correlates of the cyclic pathogenesis of CR‐EAE.

Role of Interleukin-2 and Herpes Simplex Virus 1 in Central Nervous System Demyelination in Mice

“…The presence of IL-2 is also associated with the disease state in experimental autoimmune encephalitis (EAE) (34)(35)(36) and following ocular infection of mice with HSV-1 (37-41). These observations suggest that, if IL-2 is involved, it alone may not be sufficient to initiate the observed pathology.…”

Oral Feeding with Ethinyl Estradiol Suppresses and Treats Experimental Autoimmune Encephalomyelitis in SJL Mice and Inhibits the Recruitment of Inflammatory Cells into the Central Nervous System

“…Furthermore, administration of IFN-␥ protects against demyelination and EAE (31, 32). Thus, activation, differentiation, and homing of T cells to the target tissue might be affected by the differential systemic expression of cytokines (33).…”

Mucosal administration of the B subunit of E. coli heat-labile enterotoxin promotes the development of Foxp3-expressing regulatory T cells

“…First-strand complementary DNA was synthesized using superscript complementary DNA synthesis system (Invitrogen). Reverse transcriptase-PCR was performed using primers specific for murine IL-10, 40 TGF-, 41 Foxp3, 6 and HPRT 6 (Invitrogen) as previously described using a Peltier thermal cycler (MJ Research, Waltham, MA) and 1.5 U BioTaq DNA polymerase (Bioline, London, UK). Densitometry was performed on gel images using ImageJ (US National Institutes of Health, Bethesda, MD).…”