Cutaneous antigen-stimulating lymphokine production by lymphocytes of patients with progressive systemic sclerosis (scleroderma).

Kondo, Hirobumi; Rabin, Bruce S.; Rodnan, Gerald P.

doi:10.1172/jci108594

Cited by 94 publications

(27 citation statements)

References 24 publications

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“…Results we obtained with type I collagen are in agreement with those obtained in previous studies (5,7), demonstrating little or no lymphocyte transformation. Our study did not reproduce the findings of Stuart et a1 (6).…”

Section: Discussionsupporting

confidence: 92%

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Cellular immunity to collagen and laminin in scleroderma

Huffstutter

DeLustro

LeRoy

1985

Arthritis & Rheumatism

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Peripheral blood mononuclear cells (PBMC) obtained from scleroderma patients and normal controls were cultured in the presence of types I and IV collagen, intima collagen, laminin, and phytohemagglutinin. PBMC from 9 of 19 patients (47%) demonstrated lymphocyte transformation in response to laminin, and those from 2 of 17 patients (12%) demonstrated reactivity to type IV collagen. None of the patient PBMC were responsive to type I collagen or to intima collagen. Healthy controls failed to demonstrate lymphocyte transformation in response to laminin or collagens. Analysis of clinical data, including age, disease duration, and degree of skin thickening and internal organ invollvement, failed to predict the response to laminin or type IV collagen. The significance and disease specificity of this cellular immunity to laminin and, with lower frequency, to type IV collagen, that occurs in some scleroderma patients are unknown.Scleroderma is a fibrosing disease of unknown etiology characterized by several immunologic abnor-

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Section: Discussionsupporting

confidence: 92%

“…Although the inflammatory dermal infiltrate of scleroderma has been partially characterized (2,3, IS), the stimulus for this infiltrate is unknown. Several groups of investigators (5)(6)(7)19) have observed cellular immunity to collagen, skin extracts, and certain tissue antigens.…”

Section: Discussionmentioning

confidence: 99%

Cellular immunity to collagen and laminin in scleroderma

Huffstutter

DeLustro

LeRoy

1985

Arthritis & Rheumatism

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“…Moreover, in no case except NGF did growth factors (in low serum) equal or exceed the stimulation observed with high serum. Results with NGF seemed to show equal or slightly greater stimulation with scleroderma than with control (20) or by nonspecific mitogens (21,22), leads to the elaboration of soluble factors, still poorly identified, which modulate fibroblast proliferation and collagen synthesis. The precise role of these immune events in the pathogenesis of scleroderma awaits further investigation.…”

Section: Resultsmentioning

confidence: 98%

Replication and phenotypic expression of control and scleroderma human fibroblasts: responses to growth factors.

LeRoy¹,

Mercurio²,

Sherer³

1982

Proc. Natl. Acad. Sci. U.S.A.

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To explore the mechanism of increased collagen synthesis by scleroderma skin fibroblasts in vitro, control and scleroderma fibroblasts were compared in confluent monolayer cultures growth-arrested by serum deprivation; responses to optimal mitogenic doses of platelet-derived growth factor, fibroblast growth factor, epidermal growth factor and nerve growth factor were compared. Plateletderived growth factor had a selective mitogenic effect on control skdn fibroblasts not observed with scleroderma skin fibroblasts. None of the factors studied had a selective effect on collagen synthesis independent of cell replication; scleroderma and control fibroblasts responded similarly. Therefore, the growth factors studied may not be involved in generating the activated scleroderma fibroblast directly; platelet-derived growth factor may play an indirect role in fibroblast replication in human fibrotic disorders.More than a decade ago, it was observed that fibroblasts from involved skin of patients with scleroderma synthesized increased levels of collagen in vitro (1, 2); today the mechanism remains unknown (3-6). During this period, observations ofthe pathogenesis of scleroderma have focused on vascular and microvascular lesions; on evidence of endothelial damage; on platelet adhesion, aggregation, and release; and on the subsequent activation both of smooth muscle cells to produce the intimal proliferation and of interstitial fibroblasts to produce fibrosis (7-10). A unifying hypothesis would propose the presence offactors released from plasma or platelets which act as stimuli to fibrosis; among such factors, the potent mitogen, plateletderived growth factor (PDGF), is released during endothelial injury and platelet adhesion to the subendothelium (11). Therefore, the influence of PDGF on skin fibroblast collagen synthesis was studied.Endothelial damage and platelet interaction with the exposed subendothelium, resulting in release of platelet-derived mitogenic factors (including PDGF), have been proposed, at least indirectly, to play a role in the evolution of the scleroderma vascular lesion. Events preceding endothelial injury are poorly understood; altered immunity leading to humoral or lymphocyte/monocyte mediators ofinjury has been proposed with supporting evidence (12). If PDGF is the direct mediator of fibroblast activation in scleroderma, the enhanced collagen synthesis of scleroderma fibroblasts should be accompanied by increased cell replication at some stage in the process. Thus, a PDGF mechanism in scleroderma would imply replication offibroblast populations instead of, or in addition to, the selective stimulation ofcollagen synthesis per cell; in earlier studies, increased collagen synthesis per cell was observed in vitro without evidence of increased cell replication (1, 2). If PDGF is the mediator of fibroblast activation in scleroderma, its action should account for the initial observations of increased collagen synthesis per cell.A second characteristic of scleroderma fibroblasts in culture has been ...

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“…These infiltrates have been shown to consist of either predominantly T lymphocytes (14) or of T lymphocytes and monocytes (15). PSS is known to occur with silicosis or after cosmetic surgery using foreign substances (16), and has also been noted in chronic graft-versus-host disease following bone marrow transplantation (17).…”

Section: Discussionmentioning

confidence: 99%

Enhanced production of interleukin‐2 in patients with progressive systemic sclerosis. hyperactivity of cd4‐positive t cells?

Umehara

Kumagai

Ishida

et al. 1988

Arthritis & Rheumatism

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A significant enhancement of interleukin‐2 production was observed in phytohemagglutinin‐stimulated peripheral lymphocytes from patients with progressive systemic sclerosis (PSS). Their Leu‐3a:Leu‐2a ratio was also significantly higher than normal. Moreover, Leu‐3a+ cells freshly purified from PSS patients' blood produced much more interleukin‐2 than did cells from normal subjects. These results suggest that T cell hyperactivity, especially among Leu‐3a+ T cells, occurs in patients with PSS.

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Cutaneous antigen-stimulating lymphokine production by lymphocytes of patients with progressive systemic sclerosis (scleroderma).

Cited by 94 publications

References 24 publications

Cellular immunity to collagen and laminin in scleroderma

Cellular immunity to collagen and laminin in scleroderma

Replication and phenotypic expression of control and scleroderma human fibroblasts: responses to growth factors.

Enhanced production of interleukin‐2 in patients with progressive systemic sclerosis. hyperactivity of cd4‐positive t cells?

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