T cell vaccination induces the elimination of EAE effector T cells: analysis using GFP-transduced, encephalitogenic T cells.
T cell vaccination (TCV) with irradiated encephalitogenic T cells induces resistance to EAE. However, the fate of the encephalitogenic T cells in vivo following TCV has yet to be studied. Here we used anti-MBP encephalitogenic T cells that were transduced to express GFP to study the effects of TCV on these cells. In naïve rats or in control-vaccinated (Ova-GFP) rats injected i.v. with GFP-labeled effector cells, high numbers of effector T cells were found along with macrophages, CD8 T cells and Non-GFP CD4 cells in the spleens, parathymic lymph nodes (PTLN) and spinal cords. In contrast, the recipients that had been treated with TCV (anti-MBP T-cell lines) showed few if any GFP-labeled effector T cells throughout the disease (day 1-8) and their spinal cords were almost clear of macrophages, CD4 and CD8 cells. Splenocytes in the control groups secreted IFNgamma in response to MBP and showed high numbers of IFNgamma secreting CD4 and CD8 cells in their spinal cords at the disease peak. In the TCV-protected groups, splenocytes showed no reactivity to MBP but secreted IFNgamma in response to irradiated encephalitogenic T cells--an anti-idiotypic response. Thus, TCV leads to a marked decrease in the numbers of effector T cells in the CNS and lymphoid organs, to a marked reduction in the Th1 cytokine producing cells in the CNS, and to the appearance of T cells responsive to the anti-MBP effector T cells.
Volovitz
Ilan
I
The Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel. Volovitz@yahoo.com
Marmor
Yotvat
Y
Mor
Felix
F
Flügel
Alexander
A
Odoardi
Francesca
F
Eisenbach
Lea
L
Cohen
Irun R
IR
D000818:Animals; D015704:CD4 Antigens / Q000096:biosynthesis; D016827:CD8 Antigens / Q000096:biosynthesis; D002460:Cell Line; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000517:prevention & control; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008213:Lymphocyte Activation; D008264:Macrophages / Q000473:pathology; D009103:Multiple Sclerosis / Q000276:immunology*; D004676:Myelin Basic Protein / Q000276:immunology / Q000378:metabolism*; D051381:Rats; D011917:Rats, Inbred Lew; D013116:Spinal Cord / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000637:transplantation; D014611:Vaccination
D015704:CD4 Antigens; D016827:CD8 Antigens; D004676:Myelin Basic Protein; D049452:Green Fluorescent Proteins; D007371:Interferon-gamma