022 Serum levels of interleukin-4, interleukin-10, and interleukin-13 in patients with systemic sclerosis

Hasegawa, Minoru; Takehara, Kazuhiko; Fujimoto, Mai; Kikuchi, Kenta

doi:10.1016/0923-1811(96)89424-2

Cited by 155 publications

(180 citation statements)

References 0 publications

Supporting

Mentioning

160

Contrasting

Unclassified

Order By: Relevance

“…We and other investigators have reported the existence of a predominant activation of IL-4-producing Th2-like T cells in patients with SSc, which may account for the major alterations that occur in this disease (5)(6)(7)(8).…”

mentioning

confidence: 80%

“…Both SSc and cGVHD are characterized by skin, lung, and esophageal involvement and intense fibrosis (1,2). Immunologic similarities include lymphocytic infiltration of affected tissues, the presence of Scl-70 and PM-Scl serum autoantibodies, and up-regulation of a series of cytokines (1,2,(5)(6)(7)(8). Moreover, several reports have indicated that IL-4 production by CD4ϩ T cells infiltrating SSc and cGVHD lesions is prominent in both animal models and humans, suggesting a Th2-polarized phenotype of the specific immune response in both conditions (5)(6)(7)(8)10,11).…”

Section: Discussionmentioning

confidence: 99%

“…The selected CD4ϩ T cell population derived from fetal cell engraftment may be at least partially included in the population of T cells expressing IL-4 that are found in the skin of patients with SSc (5), and it is probably responsible for the enhanced levels of IL-4 in the biologic fluids of these patients (6)(7)(8). Thus, although the results of this study need further investigation, they provide support for the hypothesis that a fetal antimaternal cGVHD may be an immunopathogenic mechanism in the development of SSc in some women.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Th2‐oriented profile of male offspring T cells present in women with systemic sclerosis and reactive with maternal major histocompatibility complex antigens

Scaletti

Vultaggio

Bonifacio

et al. 2002

Arthritis & Rheumatism

122

View full text Add to dashboard Cite

Objective. To characterize the cytokine production profile of male-offspring T cells reactive against maternal major histocompatibility complex (MHC) antigens present in the peripheral blood and/or skin from women with systemic sclerosis (SSc).Methods. T cell clones were generated from peripheral blood and/or skin biopsy specimens from 3 women with SSc of recent onset and from peripheral blood from 3 healthy women, all of whom had 1 male child. All clones were screened for their proliferative response in vitro to maternal MHC antigens by measuring 3 H-thymidine uptake and for their expression of Y chromosome by using fluorescence in situ hybridization. The concentrations of interferon-␥ and interleukin-4 (IL-4) released by T cell clones in response to maternal MHC antigens were evaluated in culture supernatants, using appropriate enzyme-linked immunosorbent assays.Results. Thirty-nine of 202 T cell clones generated from women with SSc and 11 of 312 from healthy women proliferated in vitro in response to maternal MHC antigens. Seven MHC-reactive T cell clones obtained from women with SSc and 1 obtained from healthy women exhibited the Y chromosome, thus indicating that the clones were derived from T cells of male offspring. All clones generated from male-offspring T cells of SSc women (but not from those of healthy women) produced significantly higher levels of IL-4 in response to stimulation with maternal MHC antigens than did all other clones generated from the same women. The other clones proliferated in response to maternal or allogeneic MHC antigens but did not exhibit the Y chromosome.Conclusion. Male-offspring T cells that are present in the blood and skin of women with SSc and react with maternal MHC antigens exhibit a Th2-oriented profile, supporting the possibility that a chronic graft-versus-host reaction attributable to longterm microchimerism plays a pathogenic role in SSc.

show abstract

mentioning

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Th2‐oriented profile of male offspring T cells present in women with systemic sclerosis and reactive with maternal major histocompatibility complex antigens

Scaletti

Vultaggio

Bonifacio

et al. 2002

Arthritis & Rheumatism

122

View full text Add to dashboard Cite

show abstract

“…A dominant Th2 immune response in patients with SSc has been previously reported, but the prevalence of a Th1 or a mixed immune phenotype has also been described (19,20,34,35). Importantly, the methods used to determine polarization of the immune response have been, in most cases, indirect and based on measuring highly variable parameters such as cytokine plasma levels or their mRNA expression within circulating cells or target tissues.…”

Section: T Cell Polarization In Systemic Sclerosis 1171mentioning

confidence: 99%

“…Plasma levels of IL-4 and IL-13 are elevated in SSc patients compared with healthy control subjects (19,20). Th2 cytokine expression and secretion are increased in T cells isolated from newly affected SSc skin (21,22).…”

mentioning

confidence: 99%

T cell polarization identifies distinct clinical phenotypes in scleroderma lung disease

Boin¹,

Fanis²,

Bartlett³

et al. 2008

Arthritis & Rheumatism

View full text Add to dashboard Cite

Objective. Lung involvement is the leading cause of morbidity and mortality in systemic sclerosis (SSc; scleroderma), and interstitial lung disease (ILD) is the most common pulmonary manifestation. An abnormal profibrotic Th2/Tc2-polarized T cell response is postulated to mediate tissue damage and fibrosis. The aim of this study was to investigate whether a polarized T cell phenotype in SSc is associated with lung disease or other clinical manifestations of SSc.Methods. Circulating T cells were characterized by flow cytometry in 62 patients with SSc and 36 healthy control subjects, using antibodies against CD3, CD4, CD8, chemokine receptor CCR5 (Th1/Tc1-specific), and prostaglandin D 2 receptor CRTH2 (Th2/Tc2-specific). The ratio between CCR5 and CRTH2 T cell frequencies was used to quantify type 1 (high-ratio) or type 2 (low-ratio) immune polarization.Results. Patients with SSc exhibited lower CCR5/ CRTH2 T cell ratios than those exhibited by control subjects (P < 0.0001), indicating a Th2/Tc2-polarized phenotype. Markedly reduced CCR5/CRTH2 T cell ratios were observed in SSc patients with ILD compared with SSc patients without ILD (P < 0.0001), particularly in patients with active ILD (P < 0.0001) compared with those with stable lung function. Lower CCR5/ CRTH2 ratios were strongly associated with a lower value for the percent predicted forced vital capacity (P < 0.0001). In patients with an estimated right ventricular systolic pressure >35 mm Hg, suggestive of pulmonary vascular disease, a lower value for the percent predicted diffusing capacity (DLCO) was associated with higher CCR5/CRTH2 T cell ratios (Th1/Tc1) (P ‫؍‬ 0.009), while in those with right ventricular systolic pressure <35 mm Hg, a lower value for the percent predicted DLCO correlated with lower ratios (Th2/Tc2) (P < 0.0001), as observed for ILD.

show abstract

Anti-IL-4 treatment prevents dermal collagen deposition in the tight-skin mouse model of scleroderma

et al. 1998

View full text Add to dashboard Cite

The tight-skin (Tsk/+) mutant mouse, a putative murine model of scleroderma, is characterized primarily by the excessive deposition of collagen and other extracellular matrix molecules in the dermis, and also by a developmentally acquired defect in pulmonary architecture. Passive transfer experiments have suggested an etiologic role for the immune system in Tsk/+ dermal pathology. In addition, CD4+ T lymphocytes have been shown to be required for the excessive accumulation of dermal collagen in these mice. As IL-4, a product of differentiated CD4+ T cells, is capable of regulating the synthesis of various matrix molecules (including type I collagen) by fibroblasts in vitro, we investigated the potential role of IL-4 in mediating Tsk/+ dermal fibrosis. Confirming that Tsk/+ cells are capable of responding to IL-4, we found receptors for this cytokine on Tsk/+ embryonic fibroblasts and a dermal fibroblast cell line derived from these mice. Furthermore, IL-4 receptors on Tsk/+ fibroblasts were functional since IL-4 stimulation in vitro increased type I collagen secretion from these cells. These results demonstrated the potential for IL-4 to be directly involved in the excessive deposition of dermal collagen in Tsk/+ mice. Critical insight into the role played by IL-4 in mediating the dermal phenotype, however, was obtained following the administration of neutralizing anti-lL-4 antibodies to Tsk/+ mice. This treatment prevented the development of dermal fibrosis, leading to normalization of dermal collagen content. Given the requirement for CD4+ T cells in Tsk/+ dermal fibrosis, our results suggest that Th2 cells and/or factors elaborated by this T cell subset may play a key role in regulating dermal collagen content in this strain.

show abstract

022 Serum levels of interleukin-4, interleukin-10, and interleukin-13 in patients with systemic sclerosis

Cited by 155 publications

References 0 publications

Th2‐oriented profile of male offspring T cells present in women with systemic sclerosis and reactive with maternal major histocompatibility complex antigens

Th2‐oriented profile of male offspring T cells present in women with systemic sclerosis and reactive with maternal major histocompatibility complex antigens

T cell polarization identifies distinct clinical phenotypes in scleroderma lung disease

Anti-IL-4 treatment prevents dermal collagen deposition in the tight-skin mouse model of scleroderma

Contact Info

Product

Resources

About