Inhibition by anti-HLA class II monoclonal antibodies of monoclonal antibody OKT3-induced T cell proliferation. Studies at the mRNA level.
mAb to monomorphic determinants of HLA class II Ag have been shown to inhibit monocyte-dependent OKT3-induced T cell proliferation, indicating that MHC class II molecules play a regulatory role also in Ag nonrestricted, CD3-induced T cell proliferation. This effect involves several steps in the process of T cell activation and proliferation, including IL-1 beta, IL-6, and IL-2 secretion and IL-2R alpha expression. In the present study, we analyzed the effect of an anti-HLA class II mAb (Q5/6) on the mRNA expression of genes related to monocyte and T cell activation. mRNA levels for early (early c-myc, c-fos) and late (late c-myc, N-ras, c-myb) genes involved in T cell activation were determined as well as mRNA levels for IL-1 beta, IL-6, IFN-gamma, IL-2, and IL-2R alpha. The kinetics of mRNA induction for ICAM-1 was also investigated. The results show that in T lymphocytes the expression of c-fos and early c-myc mRNA was unaffected by mAb Q5/6, whereas the c-myb and N-ras mRNA levels were strongly diminished as well as those of IL-2, IL-2R alpha, and IFN-gamma mRNA. An early increase of ICAM-1 mRNA was partially inhibited. In monocytes, a marked reduction of IL-1 beta and IL-6 mRNA was found. It is concluded that the HLA class II determinant involved in the inhibition mechanism can be engaged in the control of IL-1 beta and IL-6 mRNA levels and constitute an accessory signal up-regulating IL-2 and IL-2R alpha gene activation, through a pathway not affecting c-myc and c-fos expression.
Racioppi
L
L
Dipartimento di Biologia e Patologia Cellulare e Molecolare, Università di Napoli, Italy.
Moscarella
A
A
Ruggiero
G
G
Manzo
C
C
Ferrone
S
S
Fontana
S
S
Zappacosta
S
S
D000911:Antibodies, Monoclonal / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000235:genetics; D005786:Gene Expression Regulation; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma / Q000235:genetics; D007375:Interleukin-1 / Q000235:genetics; D007376:Interleukin-2 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D008213:Lymphocyte Activation; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000032:analysis*; D015375:Receptors, Interleukin-2 / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology*; D015533:Transcriptional Activation
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D000949:Histocompatibility Antigens Class II; D007375:Interleukin-1; D007376:Interleukin-2; D015850:Interleukin-6; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma