Susceptibility to clinically manifest cyclosporine A (CsA)-induced autoimmune disease is associated with interferon-gamma (IFN-γ)-producing CD45RC+RT6− T helper cells

Beijleveld, Leo J.J.; Groen, Herman; Broeren, Chris P. M.; Klatter, Flip A.; Kampinga, J; Damoiseaux, Jan; Vriesman, P. J. C. Van Breda

doi:10.1046/j.1365-2249.1996.d01-797.x

Cited by 25 publications

(19 citation statements)

References 38 publications

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“…This conclusion is also supported by more recent findings by Zaldivar et al (89) and Vassilakopoulous et al (84) suggesting that monocytes do not contribute significantly to augmented cytokine production following cycling exercise (30 -45 min, 75-80% V O 2peak ). Importantly, however, previous studies failed to distinguish between specific monocyte subsets, employing only single-color staining with CD14 ϩ (58, 84), CD33 ϩ (74 -77), or CD4 Dim (89) for monocyte identification, all of which are specific for the classic monocyte subset (5,12).…”

Section: Discussionmentioning

confidence: 99%

Expression of intracellular cytokines, HSP72, and apoptosis in monocyte subsets during exertional heat stress in trained and untrained individuals

Selkirk¹,

McLellan²,

Wright³

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

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Selkirk GA, McLellan TM, Wright HE, Rhind SG. Expression of intracellular cytokines, HSP72, and apoptosis in monocyte subsets during exertional heat stress in trained and untrained individuals. Am J Physiol Regul Integr Comp Physiol 296: R575-R586, 2009. First published January 21, 2009 doi:10.1152/ajpregu.90683.2008.-This study examined intracellular cytokine, heat shock protein (HSP) 72, and cellular apoptosis in classic and inflammatory CD14 ϩ monocyte subsets during exertional heat stress (EHS). Subjects were divided into endurance-trained [TR; n ϭ 12, peak aerobic power (V O2peak) ϭ 70 Ϯ 2 ml⅐ kg lean body mass (LBM) Ϫ1 ⅐ min Ϫ1 ] and sedentary-untrained (UT; n ϭ 11, V O2peak ϭ 50 Ϯ 1 ml⅐ kg LBM Ϫ1 ⅐ min Ϫ1 ) groups before walking at 4.5 km/h with 2% elevation in a climatic chamber (40°C, 30% relative humidity) wearing protective clothing until exhaustion (Exh). Venous blood samples at baseline and 0.5°C rectal temperature increments (38.0, 38.5, 39.0, 39.5, and 40.0°C/Exh) were analyzed for cytokines (TNF-␣, IL-1␤, IL-6, IL-1ra, and IL-10) in CD14 ϩϩ CD16 Ϫ /CD14 ϩ CD16 ϩ and HSP72/apoptosis in CD14 Bri / CD14 Dim subsets. In addition, serum levels of extracellular (e)HSP72 were also examined. Baseline and Exh samples were separately stimulated with LPS (1 g/ml) or heat shocked (42°C) and cultured in vitro for 2 h. A greater temperature-dependent increase in CD14 ϩ CD16 ϩ cells was observed in TR compared with UT subjects as well as a greater LPS tolerance following in vitro LPS stimulation. TNF-␣ and IL-1␤ cytokine expression was elevated in CD14 ϩ CD16 ϩ but not in CD14 ϩϩ CD16 Ϫ cells. A greater induction of intracellular HSP72 and eHSP72 was observed in TR compared with UT subjects, which coincided with reduced apoptosis at Exh and following in vitro heat shock. Induced HSP in vitro was not uniform across CD14 ϩ subsets. Findings suggest that circulating CD14 ϩ CD16 ϩ , but not CD14 ϩϩ CD16 Ϫ monocytes, contribute to the proinflammatory cytokine profiles observed during EHS. In addition, the enhanced HSP72 response in endurance-trained individuals may confer improved heat tolerance through both anti-inflammatory and anti-apoptotic mechanisms. immune function; cardiovascular/thermoregulatory strain; flow cytometry; heat shock protein PERIPHERAL BLOOD MONOCYTES play an important role in protection against invading pathogens and activation of innate immunity (46). Based on differential expression of antigenic markers CD14 [part of the LPS receptor, CD14/Toll-like receptor (TLR-4)/MD-2] and CD16 (Fc␥RIII), monocytes can be divided into two phenotypically and functionally distinct subsets (82, 90). The bulk of monocytes are defined as classic monocytes and are strongly positive for surface receptor CD14 (CD14 ϩϩ CD16 Ϫ ), whereas the minor subset are referred to as inflammatory monocytes (CD14 ϩ CD16 ϩ ) because of their high capacity to express proinflammatory cytokines such as TNF-␣ (6, 62, 64, 90). Inflammatory monocytes have the ability to respond directly with antimicrobial activity, whereas the clas...

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Section: Discussionmentioning

confidence: 99%

Expression of intracellular cytokines, HSP72, and apoptosis in monocyte subsets during exertional heat stress in trained and untrained individuals

Selkirk¹,

McLellan²,

Wright³

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

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“…By 7 days in the periphery, thymic emigrants develop to mature, Ag-naive T cells that no longer express Thy-1 and have become CD45RC and RT6 positive (7,18 . Although type 1 memory cells were not detected in LNs, 18% had a type 2 memory cell phenotype.…”

Section: Mnc Subpopulations Isolated From Lns or Sgsmentioning

confidence: 99%

Lymphocyte Lineages at Mucosal Effector Sites: Rat Salivary Glands

O’Sullivan

Skandera

Montgomery

2001

The Journal of Immunology

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Development of T cell lineages and the role of the thymus as a source of immature T cells in parotid (PG) and submandibular salivary glands (SMG) were studied in Fischer 344 rats using the Thy-1/CD45RC/RT6 expression model. In addition, the phenotypes of salivary gland lymphocytes were compared with other conventional and extrathymic populations. PG mononuclear cells consisted of T cells (38%), B cells (29%), and NK cells (4%). SMG had 19% T cells, 7% B cells, 37% NK cells, and an unusual population of CD3−/RT6+ cells. In comparison with lymph node (LN), both PG and SMG were enriched in immature (Thy-1+) and activated (Thy-1−/CD45RC−/RT6−) T cells. Unchanged percentages of Thy-1+ T cells in PG and SMG following short-term adult thymectomy indicated that immature salivary gland T cells had an extrathymic source. In contrast, thymectomy eliminated LN recent thymic emigrants. SMG had T cells with characteristics of extrathymic populations, expressing TCRγδ+ (28%), the CD8αα homodimer (11%), and NKR-P1A (66%). Many SMG T cells expressed integrin αEβ7. PG T cells resembled those isolated from LN in respect to TCR and CD8 isoform usage, but were enriched in αEβ7+ T cells and in NKT cells. Thus, salivary gland mononuclear cells are composed of a variety of subpopulations whose distributions differ between SMG and PG and are distinct from LN. These studies provide a basis for further investigation of regionalization in the mucosal immune network and are relevant to the design of vaccine regimens and intervention during pathological immune processes.

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“…In contrast, Th2-like CD45RC Ϫ CD4 ϩ T cells have been shown to suppress the progress of various autoimmune diseases including IDDM (42), inflammatory bowel disease (43), a wasting disease (44), and autoimmune graft-vs-host disease (45). Previously, we found that KRV infection in DR-BB rats increased the expression of Th1-type cytokines in the splenocytes and pancreatic infiltrates (13).…”

Section: Figurementioning

confidence: 99%

Cellular and Molecular Mechanism for Kilham Rat Virus-Induced Autoimmune Diabetes in DR-BB Rats

Chung

Jun

Son

et al. 2000

The Journal of Immunology

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Kilham rat virus (KRV) causes autoimmune diabetes in diabetes-resistant BioBreeding (DR-BB) rats; however, the mechanism by which KRV induces autoimmune diabetes without the direct infection of β cells is not well understood. We first asked whether molecular mimicry, such as a common epitope between a KRV-specific peptide and a β cell autoantigen, is involved in the initiation of KRV-induced autoimmune diabetes in DR-BB rats. We found that KRV peptide-specific T cells generated in DR-BB rats infected with recombinant vaccinia virus expressing KRV-specific structural and nonstructural proteins could not induce diabetes, indicating that molecular mimicry is not the mechanism by which KRV induces autoimmune diabetes. Alternatively, we asked whether KRV infection of DR-BB rats could disrupt the finely tuned immune balance and activate autoreactive T cells that are cytotoxic to β cells, resulting in T cell-mediated autoimmune diabetes. We found that both Th1-like CD45RC+CD4+ and cytotoxic CD8+ T cells were up-regulated, whereas Th2-like CD45RC−CD4+ T cells were down-regulated, and that isolated and activated CD45RC+CD4+ and CD8+ T cells from KRV-infected DR-BB rats induced autoimmune diabetes in young diabetes-prone BioBreeding (DP-BB) rats. We conclude that KRV-induced autoimmune diabetes in DR-BB rats is not due to molecular mimicry, but is due to a breakdown of the finely tuned immune balance of Th1-like CD45RC+CD4+ and Th2-like CD45RC−CD4+ T cells, resulting in the selective activation of β cell-cytotoxic effector T cells.

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Susceptibility to clinically manifest cyclosporine A (CsA)-induced autoimmune disease is associated with interferon-gamma (IFN-γ)-producing CD45RC+RT6− T helper cells

Cited by 25 publications

References 38 publications

Expression of intracellular cytokines, HSP72, and apoptosis in monocyte subsets during exertional heat stress in trained and untrained individuals

Expression of intracellular cytokines, HSP72, and apoptosis in monocyte subsets during exertional heat stress in trained and untrained individuals

Lymphocyte Lineages at Mucosal Effector Sites: Rat Salivary Glands

Cellular and Molecular Mechanism for Kilham Rat Virus-Induced Autoimmune Diabetes in DR-BB Rats

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