Suppression of experimental autoimmune myasthenia gravis after CD8 depletion is associated with decreased IFN-gamma and IL-4.
CD8+ T cells can perform both Th1- and Th2-like functions by producing cytokines such as interferon-gamma (IFN-gamma) and interleukin-4 (IL-4), as well as the immune response down-regulating transforming growth factor-beta (TGF-beta), which are all involved in the development of experimental autoimmune myasthenia gravis (EAMG), a model for human MG. We have reported that depletion of CD8+ T cells results in the suppression of EAMG accompanied by the down-regulation of AChR-specific B cell responses and AChR-reactive IFN-gamma secreting Th1-like cells. To identify the involvement of IFN-gamma, IL-4 and TGF-beta in the development of EAMG after CD8+ T cell depletion, the expression of mRNA for these cytokines was studied in mononuclear cells from popliteal, inguinal and mesenteric lymph nodes, spleen and thymus by adopting in situ hybridization with complementary DNA oligonucleotide probes. Depletion of CD8+ T cells resulted in decreased levels of IFN-gamma and IL-4 mRNA expressing cells in different lymphoid organs except thymus, but no change in the numbers of TGF-beta mRNA expressing cells. The results imply that the suppression of EAMG after depletion of CD8+ T cells is caused by decreasing the effector factors but not by increasing the suppressor factor(s).
Zhang
G X
GX
Division of Neurology, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden.
Ma
C G
CG
Xiao
B G
BG
Bakhiet
M
M
Ljungdahl
A
A
Olsson
T
T
Link
H
H
D000818:Animals; D015551:Autoimmunity; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002452:Cell Count; D004195:Disease Models, Animal; D015536:Down-Regulation; D005260:Female; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000096:biosynthesis*; D008221:Lymphoid Tissue / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009157:Myasthenia Gravis / Q000276:immunology* / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011917:Rats, Inbred Lew; D016212:Transforming Growth Factor beta / Q000096:biosynthesis
D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D015847:Interleukin-4; D007371:Interferon-gamma