Multiple Sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), are
autoimmune diseases driven by pathogenic memory T cells. Using myelin oligodendrocyte glycoprotein (MOG)
35-55-specific encephalitogenic T cells (TMOG) isolated from MOG35-55-immunized EAE mice we describe here their
gene expression profile following antigen specific activation. A vast number of pro-inflammatory genes including
cytokines, chemokines and growth factors (e.g., Csf2, Il3, Ccl1, Ccl3) as well as signaling pathways (e.g., iNOS,
MAPK, JAK/STAT, NFκβ) were dramatically upregulated following MOG35-55 stimulation of TMOG cells. A number of
Th17-related pathways were induced confirming potent Th17-like ac... More
Multiple Sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), are
autoimmune diseases driven by pathogenic memory T cells. Using myelin oligodendrocyte glycoprotein (MOG)
35-55-specific encephalitogenic T cells (TMOG) isolated from MOG35-55-immunized EAE mice we describe here their
gene expression profile following antigen specific activation. A vast number of pro-inflammatory genes including
cytokines, chemokines and growth factors (e.g., Csf2, Il3, Ccl1, Ccl3) as well as signaling pathways (e.g., iNOS,
MAPK, JAK/STAT, NFκβ) were dramatically upregulated following MOG35-55 stimulation of TMOG cells. A number of
Th17-related pathways were induced confirming potent Th17-like activation of TMOG. Interestingly, genes known for
their anti-inflammatory role (Sit1, Hsd11b1, Pias3, Pparg, Lgmn, Klk3, Tnfaip8l2) were down-regulated in response
to MOG35-55 suggesting that silencing of intrinsic suppressory mechanisms may underlie the hyperactivation of
memory T cells. MOG35-55 activation led to lower transcription of pro-apoptotic/autophagic genes (Ddit4, Bbc3,
Dapk2, Wbp1) and to enhanced level of anti-apoptotic transcripts (Bcl2l1). Transcripts related to toll-like receptors
and MyD88-signaling were induced, revealing the involvement of innate immunity pathways in T cell driven
autoimmunity. This study reveals the transcriptional events that lead to enhanced cytotoxicity, proliferation and
resistance to apoptosis of activated autoimmune T cells. We suggest that encephalitogenic T cells may serve as a
reliable in vitro model for screening for possible therapeutics against T cell driven autoimmune diseases.
