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

Gerfaux

et al. 1989

Arthritis & Rheumatism

The expression of c-myc, c-myb, and eras protooncogenes, determined using RNA hybridization techniques (slot-blot), was significantly increased in peripheral blood T lymphocytes, but not in B cells, from 17 patients with systemic sclerosis with diffuse scleroderma, compared with the expression in normal control subjects. The magnitude of expression of c-myc and c-myb tended to be higher in patients with early, active disease. These results demonstrate an in vivo activation of T cells from systemic sclerosis patients, which may play an important role in the pathogenesis of the disease.The etiology and pathogenesis of systemic sclerosis (SSc; scleroderma) have not been well elucidated. The disease is characterized by vascular and microvascular abnormalities (1,2), excessive fibroblastic activity (3), and collagen deposition in numerous organs (4), which might be induced by immunologic defects. A wide range of immunologic abnormalities have been described in association with SSc, including decreased numbers of circulating T lymphocytes (3, decreased From INSERM U-283 and the

Section: Discussionmentioning

confidence: 74%

Increased proto‐oncogene expression in peripheral blood T lymphocytes from patients with systemic sclerosis

Gerfaux

et al. 1989

Arthritis & Rheumatism

Clinical and Experimental Immunology

“…Previous studies have reported normal (Alcocer-Varela, Lafibn & Alarcon-Segovia, 1984) or enhanced (Umehara et al, 1988) in vitro IL-2 production in PSS patients. Most reports indicate a defective in vitro production of IL-2 in other autoimmune diseases, such as SLE (Alcocer-Varela & AlarconSegovia, 1982;Linker-Israeli et al, 1983;Miyasaka et al, 1984;Huang et al, 1988) and rheumatoid arthritis (Miyasaka et al, 1984;Kitas et al, 1988), suggesting that the in vivo activation of T cells may lead either to a state of unresponsiveness to subsequent in vitro mitogen stimulation, or to increased in vitro IL-2 utilization.…”

Section: Discussionmentioning

confidence: 88%

“…Increased serum sIL-2R levels have been reported in several autoimmune disorders, such as rheumatoid arthritis (Semenzato e;a/,, 1988;Symons e/a/,, 1988, Manoussakise^a/,, 1989), Sjogren's syndrome (Manoussakis et al, 1989), active and inactive SLE (Semenzato et al, 1988;Manoussakis et al, 1989), as well as murine lupus (Balderas et al, 1987), Since activated T lymphocytes (Uchiyama, Broder & Waldmann, 1981), B cells (Waldmann et al, 1984) and monocytes/macrophages (Hermann et al, 1985) express IL-2R, the most important cell source of elevated circulating sIL-2R levels in PSS patients remains to be determined. However, the report that at least in vitro, the amount of released sIL-2R by stimulated B lymphocytes and monocytes is less than that produced by activated T lymphocytes (Nelson et al, 1986) seems to indicate that the in vivo measurement of sIL-2R provides an accurate index of T cell activation only.…”

Section: Discussionmentioning

confidence: 99%

Soluble interleukin-2 receptor, interleukin-2 and interleukin-4 in sera and supernatants from patients with progressive systemic sclerosis

Famularo

Procopio

Giacomelli

et al. 1990

SUMMARYWe studied the sera ofpatients with progressive systemic sclerosis (PSS) for elevated levels of soluble interleukin-2 receptor (sIL-2R), interleukin-2 (IL-2) and interleukin-4 (IL-4). We also measured IL-2, IL-4 and B cell growth factor (BCGF) activity in supernatants of peripheral blood mononuclear cells from the same patients. The finding of elevated serum sIL-2R and IL-2, and the increased levels of IL-2, IL-4 and BCGF activity in culture supernatants indicates that T lymphocyte hyperactivity likely play a major role in PSS. The failure to detect under our exjjerimental conditions a direct proliferative effect of recombinant IL-2 on enriched normal B cells might suggest that IL-4 is the cytokine mainly responsible of the BCGF activity recovered in PSS supernatants.Keywords progressive systemic sclerosis soluble interleukin-2 receptor interleukin-2 interleukin-4 B cell growth factor activity

Clinical and Experimental Immunology

“…T cells and non-T cells were separated by rosetting method with sheep erythroeytes, as previously described [14]. The T cell preparations contained >94% CD3^ cells in both normal subjects and SSc patients.…”

Section: Amlrmentioning

confidence: 99%

“…patients were hyperactive because of their hyperproduction of IL-2 [14]. In contrast, the autologous mixed lymphocyte reaction (AMLR) of SSc patients was unique, because their T cells showed early but decreased proliferative responses compared with those of normal controls [15].…”

Section: Introductionmentioning

confidence: 99%

Enhanced production of transforming growth factor-beta (TGF-β) during autologous mixed lymphocyte reaction of systemic sclerosis patients

Ôta

Kumagai

Morinobu

et al. 1995

SUMMARY Systemic sclerosis (SSc) is characterized by systemic fibrosis and microvascular lesions. As TGF‐β is suggested to be related to skin fibrosis, we examined the production of TGF‐β from peripheral mononuclear cells (MNC) of SSc patients. Since anti‐TGF‐β neutralizing antibody improved the defective proliferative response in autologous mixed lymphocyte reaction (AMLR) of SSc patients, TGF‐β was thought to participate in the decreased AMLR of SSc patients. Greater amounts of TGF‐β in the active as well as in the latent forms were produced during AMLR of SSc patients than that of normal subjects. It was suggested that TGF‐β excessively produced from the MNC of SSc patients might play a major role in the fibrosis of the patients during AMLR‐like in vivo responses.