Inhibition of type I collagen production by dermal fibroblasts upon contact with activated T cells: different sensitivity to inhibition between systemic sclerosis and control fibroblasts.
OBJECTIVE
To assess the role of T lymphocyte-fibroblast contact in type I collagen production by cultured dermal fibroblasts from normal individuals and from patients with diffuse systemic sclerosis (SSc).


METHODS
Cell membranes were prepared from activated CD4+ and CD8+ T cells, or type 1 T helper (Th1) clones, and added to confluent fibroblast monolayers. Type I collagen production was measured in culture supernatants, and messenger RNA (mRNA) levels of type I procollagen alpha1 (pro alpha1[I]) and matrix metalloproteinase 1 (MMP-1) were evaluated by Northern hybridization analysis.


RESULTS
Dose-dependent inhibition of type I collagen production was observed with CD4+ and CD8+ T cells from both SSc patients and controls. Inhibition of type I collagen was significantly less pronounced in fibroblasts from SSc patients than in fibroblasts from controls (P < 0.02). Inhibition was not reversed by the addition of exogenous transforming growth factor beta, interleukin-4, interleukin-1 receptor antagonist, anti-tumor necrosis factor, anti-CD40, or indomethacin, whereas anti-interferon-gamma (IFNgamma) reversed Th1-mediated inhibition. This inhibitory activity was specific for type I collagen, since mRNA levels of pro alpha1(I) were decreased, whereas mRNA levels of MMP-1 were strongly increased.


CONCLUSIONS
The production of type I collagen by skin fibroblasts is specifically down-regulated by membranes from activated T cells. The contact-dependent regulatory activity exerted by T cells on fibroblasts depends, at least in part, on the presence of membrane-associated IFNgamma. However, SSc fibroblasts are more resistant to inhibition than are fibroblasts from normal individuals.
Chizzolini
C
C
University Hospital, Geneva, Switzerland.
Rezzonico
R
R
Ribbens
C
C
Burger
D
D
Wollheim
F A
FA
Dayer
J M
JM
D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002450:Cell Communication / Q000276:immunology; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D003094:Collagen / Q000235:genetics / Q000276:immunology*; D017364:Collagenases / Q000235:genetics; D005109:Extracellular Matrix / Q000737:chemistry / Q000276:immunology; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008297:Male; D020781:Matrix Metalloproteinase 1; D008875:Middle Aged; D011347:Procollagen / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D012595:Scleroderma, Systemic / Q000276:immunology*; D012867:Skin / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*
D011347:Procollagen; D012333:RNA, Messenger; D015847:Interleukin-4; D007371:Interferon-gamma; D003094:Collagen; D017364:Collagenases; D020781:Matrix Metalloproteinase 1