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Up-regulation of alternate co-stimulatory molecules on proinflammatory CD28null T cells in bronchiolitis obliterans syndrome.
Clin Exp Immunol. 2013 Jul; 173(1):150-60.CE

Abstract

Bronchiolitis obliterans syndrome (BOS) is associated with lack of immunosuppression of T cell proinflammatory cytokines and increased T cell granzyme B. Repeated antigen-driven proliferation down-regulates T cell CD28. We hypothesized that down-regulation of CD28 and up-regulation of alternate co-stimulatory molecules (CD134, CD137, CD152 and CD154) on T cells may be associated with BOS. Co-stimulatory molecules, granzyme B, perforin and intracellular cytokines were measured by flow cytometry on T cells from stable lung transplant patients (n = 38), patients with BOS (n = 20) and healthy controls (n = 10). There was a significant increase in the percentage of CD4/28(null) and CD8/28(null) T cells producing granzyme B, interferon (IFN)-γ and tumour necrosis factor (TNF)-α in BOS compared with stable patients. Down-regulation of CD28 was associated with steroid resistance and up-regulation of CD134, CD137, CD152 and CD154 on CD4(+) T cells and CD137 and CD152 on CD8(+) T cells. There was a significant correlation between increased CD28(null) /CD137 T cells producing IFN-γ, TNF-α with BOS grade (r = 0·861, P < 0·001 for CD28(null) /CD137 IFN-γ/CD8) and time post-transplant (r = 0·698, P < 0·001 for CD28(null) /CD137 IFN-γ/CD8). BOS is associated with down-regulation of CD28 and up-regulation of alternate co-stimulatory molecules on steroid-resistant peripheral blood proinflammatory CD4(+) and CD8(+) T cells. Therapeutic targeting of alternate co-stimulatory molecules on peripheral blood CD28(null) T cells and monitoring response using these assays may help in the management of patients with BOS.

Authors+Show Affiliations

Lung Research, Hanson Institute and Department of Thoracic Medicine, Royal Adelaide Hospital, Australia. greg.hodge@health.sa.gov.auNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23607447

Citation

Hodge, G, et al. "Up-regulation of Alternate Co-stimulatory Molecules On Proinflammatory CD28null T Cells in Bronchiolitis Obliterans Syndrome." Clinical and Experimental Immunology, vol. 173, no. 1, 2013, pp. 150-60.
Hodge G, Hodge S, Ahern J, et al. Up-regulation of alternate co-stimulatory molecules on proinflammatory CD28null T cells in bronchiolitis obliterans syndrome. Clin Exp Immunol. 2013;173(1):150-60.
Hodge, G., Hodge, S., Ahern, J., Holmes-Liew, C. L., Reynolds, P. N., & Holmes, M. (2013). Up-regulation of alternate co-stimulatory molecules on proinflammatory CD28null T cells in bronchiolitis obliterans syndrome. Clinical and Experimental Immunology, 173(1), 150-60. https://doi.org/10.1111/cei.12081
Hodge G, et al. Up-regulation of Alternate Co-stimulatory Molecules On Proinflammatory CD28null T Cells in Bronchiolitis Obliterans Syndrome. Clin Exp Immunol. 2013;173(1):150-60. PubMed PMID: 23607447.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Up-regulation of alternate co-stimulatory molecules on proinflammatory CD28null T cells in bronchiolitis obliterans syndrome. AU - Hodge,G, AU - Hodge,S, AU - Ahern,J, AU - Holmes-Liew,C-L, AU - Reynolds,P N, AU - Holmes,M, PY - 2013/01/21/accepted PY - 2013/4/24/entrez PY - 2013/4/24/pubmed PY - 2013/8/6/medline SP - 150 EP - 60 JF - Clinical and experimental immunology JO - Clin Exp Immunol VL - 173 IS - 1 N2 - Bronchiolitis obliterans syndrome (BOS) is associated with lack of immunosuppression of T cell proinflammatory cytokines and increased T cell granzyme B. Repeated antigen-driven proliferation down-regulates T cell CD28. We hypothesized that down-regulation of CD28 and up-regulation of alternate co-stimulatory molecules (CD134, CD137, CD152 and CD154) on T cells may be associated with BOS. Co-stimulatory molecules, granzyme B, perforin and intracellular cytokines were measured by flow cytometry on T cells from stable lung transplant patients (n = 38), patients with BOS (n = 20) and healthy controls (n = 10). There was a significant increase in the percentage of CD4/28(null) and CD8/28(null) T cells producing granzyme B, interferon (IFN)-γ and tumour necrosis factor (TNF)-α in BOS compared with stable patients. Down-regulation of CD28 was associated with steroid resistance and up-regulation of CD134, CD137, CD152 and CD154 on CD4(+) T cells and CD137 and CD152 on CD8(+) T cells. There was a significant correlation between increased CD28(null) /CD137 T cells producing IFN-γ, TNF-α with BOS grade (r = 0·861, P < 0·001 for CD28(null) /CD137 IFN-γ/CD8) and time post-transplant (r = 0·698, P < 0·001 for CD28(null) /CD137 IFN-γ/CD8). BOS is associated with down-regulation of CD28 and up-regulation of alternate co-stimulatory molecules on steroid-resistant peripheral blood proinflammatory CD4(+) and CD8(+) T cells. Therapeutic targeting of alternate co-stimulatory molecules on peripheral blood CD28(null) T cells and monitoring response using these assays may help in the management of patients with BOS. SN - 1365-2249 UR - https://www.unboundmedicine.com/medline/citation/23607447/Up_regulation_of_alternate_co_stimulatory_molecules_on_proinflammatory_CD28null_T_cells_in_bronchiolitis_obliterans_syndrome_ L2 - https://doi.org/10.1111/cei.12081 DB - PRIME DP - Unbound Medicine ER -