Journal article
Inhibition of pro-inflammatory cytokine generation by CTLA4-Ig in the skin and colon of mice adoptively transplanted with CD45RB hi CD4 + T cells correlates with suppression of psoriasis and colitis
International immunopharmacology, v 2(5), pp 653-672
2002
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Transfer of CD45RB
hi CD4
+ naı̈ve T cells into severe combined immunodeficient (SCID) mice induces colitis and skin lesions. Recipients treated with cyclosporin A (CsA), CTLA4-Ig, or vehicle were evaluated for weight loss, skin lesions, and cutaneous blood flow. Necropsy, histological, hematological and cytokine analyses were performed at the conclusion of the experiment to confirm the clinical findings. Vehicle-treated mice lost weight and had 100% incidence of skin lesions by 46-days. CsA-treated mice also lost weight, but only 3/8 mice developed mild, clinically evident skin lesions. In contrast, all CTLA4-Ig-treated mice gained weight and did not develop skin lesions. Increase in cutaneous blood flow correlated with the development of skin lesions. Granulocyte numbers, which were high or moderately high in the vehicle- or CsA-treated mice, respectively, remained as low in the CTLA4-Ig-treated group as in untreated mice. IFN-γ, IL-1β, and TNF-α levels in the gut and skin correlated with the extent of inflammation in both organs. Histology revealed that CTLA4-Ig but not CsA effectively prevented both autoimmune disorders. The ability of CTLA4-Ig to prevent both colitis and skin lesions suggests that CD28-dependent co-stimulation of T cells is critical for generation of pro-inflammatory cytokines and induction of clinical disease in such autoimmune disorders.
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Details
- Title
- Inhibition of pro-inflammatory cytokine generation by CTLA4-Ig in the skin and colon of mice adoptively transplanted with CD45RB hi CD4 + T cells correlates with suppression of psoriasis and colitis
- Creators
- Colleen M Davenport - GlaxoSmithKlineHolly Ann McAdams - GlaxoSmithKlineJen Kou - GlaxoSmithKlineKirsten Mascioli - GlaxoSmithKlineChristopher Eichman - GlaxoSmithKlineLaura Healy - GlaxoSmithKlineJohn Peterson - GlaxoSmithKlineSreekant Murphy - Hahnemann University HospitalDomenico Coppola - University of South FloridaAlemseged Truneh - GlaxoSmithKlineSara N Murphy - A.J. Drexel Autism Institute
- Publication Details
- International immunopharmacology, v 2(5), pp 653-672
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- A.J. Drexel Autism Institute
- Web of Science ID
- WOS:000175179200004
- Scopus ID
- 2-s2.0-18344391018
- Other Identifier
- 991019167723504721
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- Collaboration types
- Industry collaboration
- Domestic collaboration
- Web of Science research areas
- Immunology
- Pharmacology & Pharmacy