Abnormal T cells from lpr mice down-regulate transcription of interferon-gamma and tumor necrosis factor-alpha in vitro.
We have studied the ability of isolated T cell subpopulations from the autoimmune mouse MRL/MPJ/lpr/lpr (lpr) to proliferate and to undergo changes in cytokine gene transcription in vitro, in the presence or absence of cytokines. The lpr mouse develops lupus-like symptoms and massive lymphadenopathy due to accumulation of abnormal CD4-/CD8- T lymphocytes, which are unusual in coexpressing Thy1 and B220. FACS-purified B220+/Thy1+ lpr lymph node cells showed little proliferative response to cytokines, even in the presence of PMA, and failed to proliferate in response to stimulation through the CD3/TcR complex. Polymerase chain reaction was used to examine the presence of cytokine gene transcripts in B220-/Thy1+ and B220+/Thy1+ ("abnormal") T cells, before and after in vitro culture. The high level of transcripts of IFN-gamma and TNF-alpha genes observed in freshly isolated B220+/Thy1+ cells decreased after 10 hr of in vitro culture, while levels of TNF-beta, IL-6 and TGF-beta transcripts were maintained. These results suggest that a positive stimulus for IFN-gamma and TNF-alpha gene transcription by lpr B220+/Thy1+ cells may exist in vivo but is removed upon purification of this abnormal T cell subset.
Murray
L
L
DNAX Research Institute, Palo Alto, California 94304-1104.
Martens
C
C
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis / Q000502:physiology; D001327:Autoimmune Diseases / Q000276:immunology*; D001685:Biological Factors / Q000494:pharmacology; D017252:CD3 Complex; D016827:CD8 Antigens; D002478:Cells, Cultured; D016207:Cytokines; D015536:Down-Regulation; D015870:Gene Expression; D007371:Interferon-gamma / Q000235:genetics*; D007378:Interleukins / Q000235:genetics; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D051379:Mice; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D013601:T-Lymphocytes / Q000502:physiology*; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D000945:Antigens, Differentiation, T-Lymphocyte; D001685:Biological Factors; D017252:CD3 Complex; D016827:CD8 Antigens; D016207:Cytokines; D007378:Interleukins; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma