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Intracellular cytokines in blood T cells in lung transplant patients--a more relevant indicator of immunosuppression than drug levels.
Clin Exp Immunol. 2005 Jan; 139(1):159-64.CE

Abstract

Allograft rejection remains a major cause of morbidity and mortality following lung transplantation and is associated with an increase in T-cell pro-inflammatory cytokine expression. Systemic levels of immunosuppressive drugs used to reduce pro-inflammatory cytokine expression are closely monitored to their 'therapeutic range'. However, it is currently unknown if levels of these drugs correlate with pro-inflammatory cytokine expression in peripheral blood T cells. To investigate the immunomodulatory effects of currently used immunosuppressive regimes on peripheral blood T-cell cytokine production, whole blood from stable lung transplant patients and control volunteers were stimulated in vitro and cytokine production by CD8+ and CD4+ T-cell subsets determined using multiparameter flow cytometry. T-cell IL-2 and TNFalpha production was significantly reduced from lung transplant patients compared to controls. CD4+ T-cell production of IFNgamma was also significantly reduced from lung transplant patients but production of IFNgamma by CD8+ T cells remained unchanged. There was an excellent correlation between the percentage of CD8+ T cells and the percentage of CD8+ T cells producing IFNgamma from transplant patients. T-cell IL-4 and CD8+ T-cell production of TGFbeta was significantly increased from lung transplant patients. We now provide evidence that current immunosuppression protocols have limited effect on peripheral blood IFNgamma production by CD8+ T-cells but do up-regulate T-cell anti-inflammatory cytokines. Drugs that effectively reduce IFNgamma production by CD8+ T cells may improve current protocols for reducing graft rejection in these patients. Intracellular cytokine analysis using flow cytometry may be a more appropriate indicator of immunosuppression than drug levels in these patients. This technique may prove useful in optimizing therapy for individual patients.

Authors+Show Affiliations

Department of Thoracic Medicine, Royal Adelaide Hospital, Adelaide, South Australia. hodgeg@mail.wch.sa.gov.auNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

15606627

Citation

Hodge, G, et al. "Intracellular Cytokines in Blood T Cells in Lung Transplant Patients--a More Relevant Indicator of Immunosuppression Than Drug Levels." Clinical and Experimental Immunology, vol. 139, no. 1, 2005, pp. 159-64.
Hodge G, Hodge S, Reynolds P, et al. Intracellular cytokines in blood T cells in lung transplant patients--a more relevant indicator of immunosuppression than drug levels. Clin Exp Immunol. 2005;139(1):159-64.
Hodge, G., Hodge, S., Reynolds, P., & Holmes, M. (2005). Intracellular cytokines in blood T cells in lung transplant patients--a more relevant indicator of immunosuppression than drug levels. Clinical and Experimental Immunology, 139(1), 159-64.
Hodge G, et al. Intracellular Cytokines in Blood T Cells in Lung Transplant Patients--a More Relevant Indicator of Immunosuppression Than Drug Levels. Clin Exp Immunol. 2005;139(1):159-64. PubMed PMID: 15606627.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Intracellular cytokines in blood T cells in lung transplant patients--a more relevant indicator of immunosuppression than drug levels. AU - Hodge,G, AU - Hodge,S, AU - Reynolds,P, AU - Holmes,M, PY - 2004/12/21/pubmed PY - 2005/3/3/medline PY - 2004/12/21/entrez SP - 159 EP - 64 JF - Clinical and experimental immunology JO - Clin. Exp. Immunol. VL - 139 IS - 1 N2 - Allograft rejection remains a major cause of morbidity and mortality following lung transplantation and is associated with an increase in T-cell pro-inflammatory cytokine expression. Systemic levels of immunosuppressive drugs used to reduce pro-inflammatory cytokine expression are closely monitored to their 'therapeutic range'. However, it is currently unknown if levels of these drugs correlate with pro-inflammatory cytokine expression in peripheral blood T cells. To investigate the immunomodulatory effects of currently used immunosuppressive regimes on peripheral blood T-cell cytokine production, whole blood from stable lung transplant patients and control volunteers were stimulated in vitro and cytokine production by CD8+ and CD4+ T-cell subsets determined using multiparameter flow cytometry. T-cell IL-2 and TNFalpha production was significantly reduced from lung transplant patients compared to controls. CD4+ T-cell production of IFNgamma was also significantly reduced from lung transplant patients but production of IFNgamma by CD8+ T cells remained unchanged. There was an excellent correlation between the percentage of CD8+ T cells and the percentage of CD8+ T cells producing IFNgamma from transplant patients. T-cell IL-4 and CD8+ T-cell production of TGFbeta was significantly increased from lung transplant patients. We now provide evidence that current immunosuppression protocols have limited effect on peripheral blood IFNgamma production by CD8+ T-cells but do up-regulate T-cell anti-inflammatory cytokines. Drugs that effectively reduce IFNgamma production by CD8+ T cells may improve current protocols for reducing graft rejection in these patients. Intracellular cytokine analysis using flow cytometry may be a more appropriate indicator of immunosuppression than drug levels in these patients. This technique may prove useful in optimizing therapy for individual patients. SN - 0009-9104 UR - https://www.unboundmedicine.com/medline/citation/15606627/Intracellular_cytokines_in_blood_T_cells_in_lung_transplant_patients__a_more_relevant_indicator_of_immunosuppression_than_drug_levels_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0009-9104&date=2005&volume=139&issue=1&spage=159 DB - PRIME DP - Unbound Medicine ER -