Premium
Regulation of cytokine gene expression in experimental autoimmune encephalomyelitis
Author(s) -
Zitron Ian M.,
Reddy B. Praveen,
Gould Karen E.,
Stephanik Jolie A.,
Swanborg Robert H.
Publication year - 1996
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/(sici)1097-4547(19961115)46:4<438::aid-jnr5>3.0.co;2-h
Subject(s) - experimental autoimmune encephalomyelitis , messenger rna , myelin basic protein , microbiology and biotechnology , biology , secretion , cytokine , spleen , antigen , immunology , immune system , gene , myelin , endocrinology , central nervous system , biochemistry
We previously reported that recovery of Lewis rats from experimental autoimmune encephalomyelitis (EAE) is associated with the appearance of suppressor T cells (Ts). These Ts secrete TGF‐β which down‐regulates the production of inflammatory cytokines by the effector T cells that mediate this disease. In the present study, we immunized Lewis rats with myelin basic protein (MBP) + CFA, and evaluated purified T cells and MBP‐activated spleen cells (SpC) during the paralytic phase (day 12) and after recovery (days 30‐33) for TGF‐β and interferon (IFN)‐γ mRNA. We used reverse transcriptase‐polymerase chain reaction (RT‐PCR), quantitated on the basis of β‐actin mRNA. Abundant IFN‐γ mRNA was present in MBP‐activated SpC obtained on day 12. In contrast, only trace IFN‐γ mRNA was detected in day 30 activated SpC, and no IFN‐γ mRNA was present in purified, nonactivated T cells obtained at either time. The level of IFN‐γ mRNA correlated with secretion of IFN‐γ as determined by ELISA on SpC culture supernatants, and with severity of adoptively transferred EAE by the activated SpC. Thus, it appears that IFN‐γ mRNA is both transcribed and translated in response to antigen activation, resulting in secretion of IFN‐γ by the disease‐inducing Te. In contrast, when we used RT‐PCR to investigate the expression of TGF‐β mRNA, we found the transcript present in isolated T cells and MBP‐activated SpC obtained from rats at both days 12 and 30. The presence of TGF‐β mRNA at time points corresponding to both clinical EAE and recovery suggests post‐transcriptional regulation of the production of this immunoregulatory cytokine. © 1996 Wiley‐Liss, Inc.