liu.seSearch for publications in DiVA
Change search
Link to record
Permanent link

Direct link
BETA
Backteman, Karin
Publications (10 of 15) Show all publications
Backteman, K., Ernerudh, J. & Jonasson, L. (2014). Cytomegalovirus seropositivity is a major determinant of CD28null T cell expansion in patients with coronary artery disease.
Open this publication in new window or tab >>Cytomegalovirus seropositivity is a major determinant of CD28null T cell expansion in patients with coronary artery disease
2014 (English)Manuscript (preprint) (Other academic)
Abstract [en]

Objective: Accumulation of CD4+28null cells, with a proinflammatory and senescent phenotype, has been associated with unstable conditions of coronary artery disease (CAD). Human cytomegalovirus (HCMV) is known to exert profound effects on T cells, including loss of CD28. Here, we longitudinally assessed the proportions of CD28null and CD28nullCD57+ cells in CD4+ and CD8+ T cell populations of patients with CAD and related the findings to HCMV seropositivity.

Methods: HCMV antibody levels and expression of CD28 and CD57 on CD4+ and CD8+ T cells were analysed in 31 patients with acute coronary syndrome (ACS), 34 patients with stable angina (SA) and 37 healthy controls. Samples were taken prior to 34 coronary angiography and after 3 and 12 months. In a subsample, HCMV-specific IFN-γ and  TNF production was assessed ex vivo.

Results: Increased proportions of CD4+CD28null, but not CD8+CD28null cells, were significantly associated with presence of CAD. Significant increases in CD28null 37 and CD28nullCD57+ cells occurred within CD4+ and CD8+ T cell compartments in both ACS and SA patients during 12-month follow-up. HCMV was the major determinant of CD28null and CD28nullCD57+ T cell levels in both patients and controls (p <0.001). There were no obvious signs of CMV reactivation in patients.

Conclusion: HCMV was a major determinant of the presence of CD28null and CD28nullCD57+ T cells in patients with CAD, independent of clinical stage. Findings also indicate that HCMV might have a large impact on the T cell aging process that occurred in patients after a cardiac event.

Keywords
Coronary artery disease, acute coronary syndrome, CD28null T cells, CD57+ 49 T cells, Human cytomegalovirus
National Category
Clinical Medicine Immunology
Identifiers
urn:nbn:se:liu:diva-111049 (URN)
Available from: 2014-10-06 Created: 2014-10-06 Last updated: 2015-03-25Bibliographically approved
Backteman, K., Ernerudh, J. & Jonasson, L. (2014). Natural killer (NK) cell deficit in coronary artery disease: no aberrations in phenotype but sustained reduction of NK cells is associated with low-grade inflammation. Clinical and Experimental Immunology, 175(1), 104-112
Open this publication in new window or tab >>Natural killer (NK) cell deficit in coronary artery disease: no aberrations in phenotype but sustained reduction of NK cells is associated with low-grade inflammation
2014 (English)In: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 175, no 1, p. 104-112Article in journal (Refereed) Published
Abstract [en]

Although reduced natural killer (NK) cell levels have been reported consistently in patients with coronary artery disease (CAD), the clinical significance and persistence of this immune perturbation is not clarified. In this study we characterized the NK cell deficit further by determining (i) differentiation surface markers and cytokine profile of NK cell subsets and (ii) ability to reconstitute NK cell levels over time. Flow cytometry was used to analyse NK cell subsets and the intracellular cytokine profile in 31 patients with non-ST elevation myocardial infarction (non-STEMI), 34 patients with stable angina (SA) and 37 healthy controls. In blood collected prior to coronary angiography, the proportions of NK cells were reduced significantly in non-STEMI and SA patients compared with controls, whereas NK cell subset analyses or cytokine profile measurements did not reveal any differences across groups. During a 12-month follow-up, the proportions of NK cells increased, although not in all patients. Failure to reconstitute NK cell levels was associated with several components of metabolic syndrome. Moreover, interleukin (IL)-6 levels remained high in patients with sustained NK cell deficit, whereas a decline in IL-6 (P < 0·001) was seen in patients with a pronounced increase in NK cells. In conclusion, we found no evidence that reduction of NK cells in CAD patients was associated with aberrations in NK cell phenotype at any clinical stage of the disease. Conversely, failure to reconstitute NK cell levels was associated with a persistent low-grade inflammation, suggesting a protective role of NK cells in CAD.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2014
Keywords
coronary artery disease; cytokines; inflammation; leukocytes; natural killer cell
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-103363 (URN)10.1111/cei.12210 (DOI)000329165400012 ()24298947 (PubMedID)
Available from: 2014-01-17 Created: 2014-01-17 Last updated: 2017-12-06Bibliographically approved
Szymanowski, A., Li, W., Lundberg, A., Evaldsson, C., Nilsson, L., Backteman, K., . . . Jonasson, L. (2014). Soluble Fas ligand is associated with natural killer cell dynamics in coronary artery disease. Atherosclerosis, 233(2), 616-622
Open this publication in new window or tab >>Soluble Fas ligand is associated with natural killer cell dynamics in coronary artery disease
Show others...
2014 (English)In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 233, no 2, p. 616-622Article in journal (Refereed) Published
Abstract [en]

Objective: Apoptosis of natural killer (NK) cells is increased in patients with coronary artery disease (CAD) and may explain why NK cell levels are altered in these patients. Soluble forms of Fas and Fas ligand (L) are considered as markers of apoptosis. Here, we investigated whether plasma levels of Fas and FasL were associated with NK cell apoptosis and NK cell levels in CAD patients. Methods: Fas and FasL in plasma were determined by ELISA in 2 cohorts of CAD patients; one longitudinal study measuring circulating NK cells and apoptotic NK cells by flow cytometry 1 day, 3 months and 12 months after a coronary event and one cross-sectional study measuring NK cell apoptosis ex vivo. Both studies included matched healthy controls. Fas and FasL were also determined in supernatants from NK cells undergoing cytokine-induced apoptosis in cell culture. Results: In the 12-month longitudinal study, plasma FasL increased by 15% (p less than 0.001) and NK cell levels by 31% (p less than 0.05) while plasma Fas did not change. Plasma FasL and NK cell levels were significantly related at 3 months and 12 months, r = 0.40, p less than 0.01. Furthermore, plasma FasL, but not plasma Fas, correlated with NK cell apoptosis ex vivo in CAD patients, r = 0.54, p less than 0.05. In vitro, cytokine-induced apoptosis of NK cells resulted in abundant release of FasL. Conclusion: In CAD patients, FasL in plasma is associated with both apoptotic susceptibility of NK cells and dynamic changes in circulating NK cells. NK cells are also themselves a potential source of soluble FasL. Our findings link NK cell status to a soluble marker with possible atheroprotective effects thereby supporting a beneficial role of NK cells in CAD.

Place, publisher, year, edition, pages
Elsevier, 2014
Keywords
Acute coronary syndrome; Coronary artery disease; Immune system; Leukocytes; Natural killer cells; Apoptosis
National Category
Cardiac and Cardiovascular Systems Cell and Molecular Biology
Identifiers
urn:nbn:se:liu:diva-106858 (URN)10.1016/j.atherosclerosis.2014.01.030 (DOI)000334337200045 ()
Available from: 2014-05-28 Created: 2014-05-23 Last updated: 2018-01-11
Backteman, K. (2014). T Cells and NK Cells in Coronary Artery Disease: Longitudinal and methodological studies in humans. (Doctoral dissertation). Linköping: Linköping University Electronic Press
Open this publication in new window or tab >>T Cells and NK Cells in Coronary Artery Disease: Longitudinal and methodological studies in humans
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Coronary artery disease (CAD) is the leading cause of death worldwide and most often due to atherosclerosis. Atherosclerosis is a chronic inflammatory process that involves the arteries, inclouding those that supply blood to the heart muscle. Although inflammation is an important contributing factor to atherosclerosis, the mechanisms are not fully understood. One mechanism contributing to atherogenesis may involve some infectious microorganisms such as cytomegalovirus (CMV). In atherosclerosis, the arterial wall becomes infiltrated with lipids followed by different types of leukocytes and inflammatory mediators (atherogenesis). Leukocytes recirculate continuously between the blood and lymphoid organs, such as lymph nodes, where the adaptive immune response is started and regulated.

The general aim of this thesis was to increase the understanding of associations between lymphocyte populations and different conditions of CAD (unstable and stable). To assess changes over time, a longitudinal follow up design was mostly used. Therefore, also perspectives of longitudinal variation were included in the thesis.

Paper I showed that flow cytometric evaluation of lymphocyte populations is a robust technique that can be used in longitudinal studies, both in clinical and research settings. It was also shown that the time of sampling over the year did not have a major impact on the findings.

In paper II, thoracic lymph nodes were investigated to assess whether CAD-associated changes were more prominent in comparison with blood. As expected, there were several major differences in lymphocyte composition between lymph nodes and blood. However, the analysis of thoracic lymph nodes did not reveal any further changes that were not detected in blood. Thus, blood is still the most reliable compartment for studies of lymphocyte populations in CAD since it is not possible to examine the local findings in the artery wall.

Natural killer (NK) cells are innate lymphocytes with both regulatory and effector functions. In paper II and III we confirmed previous findings that CAD patients have lower proportions of NK cells in blood. However, the NK subtype and cytokine profile (paper III, measured by subtype markers and intra-cellular cytokine staining) did not differ between patients and controls. During a 12-month follow-up, the proportions of NK cells increased, although not in all patients. Failure to reconstitute NK cell levels was associated with several components of the metabolic syndrome and with a persistent low-grade inflammation as measured by plasma IL-6 levels. The findings support the notion of a protective role for NK cells in inflammation.

CD4+ but not CD8+ T cells were significantly increased in patients with both unstable and stable conditions compared with healthy individuals (paper IV). Subpopulations of CD4+ T cells (CD4+CD28null) have previously been associated with CAD. However, we show that CD28null and CD28null57+ cells within the CD4+ and CD8+ T cell populations were similar in CAD patients and healthy controls. Instead, CMV seropositivity was the major determinant of expanded CD28null and CD57+ T cell fractions in both patients and healthy individuals. During the 1 year follow up the proportion of CD4+CD28null and CD8+CD28null cells increased in patients, which may reflect an accelerated immunological ageing occurring after the cardiac event.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2014. p. 85
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1409
National Category
Immunology Cell Biology
Identifiers
urn:nbn:se:liu:diva-111050 (URN)10.3384/diss.diva-111050 (DOI)978-91-7519-303-8 (ISBN)
Public defence
2014-11-07, Berzeliussalen, Campus US, Linköpings universitet, Linköping, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2014-10-06 Created: 2014-10-06 Last updated: 2014-10-06Bibliographically approved
Backteman, K., Andersson, C., Ernerudh, J. & Jonasson, L. (2012). Lymphocyte Subpopulations in Lymph Nodes and Peripheral Blood: A Comparison between Patients with Stable Angina and Acute Coronary Syndrome. PLoS ONE, 7(3)
Open this publication in new window or tab >>Lymphocyte Subpopulations in Lymph Nodes and Peripheral Blood: A Comparison between Patients with Stable Angina and Acute Coronary Syndrome
2012 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 3Article in journal (Refereed) Published
Abstract [en]

Objective: Atherosclerosis is characterized by a chronic inflammatory response involving activated T cells and impairment of natural killer (NK) cells. An increased T cell activity has been associated with plaque instability and risk of acute cardiac events. Lymphocyte analyses in blood are widely used to evaluate the immune status. However, peripheral blood contains only a minor proportion of lymphocytes. In this study, we hypothesized that thoracic lymph nodes from patients with stable angina (SA) and acute coronary syndrome (ACS) might add information to peripheral blood analyses. less thanbrgreater than less thanbrgreater thanMethods: Peripheral blood and lymph nodes were collected during coronary by-pass surgery in 13 patients with SA and 13 patients with ACS. Lymphocyte subpopulations were assessed by flow cytometry using antibodies against CD3, CD4, CD8, CD19, CD16/56, CD25, Foxp3, CD69, HLA-DR, IL-18 receptor (R) and CCR4. less thanbrgreater than less thanbrgreater thanResults: Lymph nodes revealed a lymphocyte subpopulation profile substantially differing from that in blood including a higher proportion of B cells, lower proportions of CD8(+) T cells and NK cells and a 2-fold higher CD4/CD8 ratio. CD4(+)CD69(+) cells as well as Foxp3(+) regulatory T cells were markedly enriched in lymph nodes (p andlt; 0.001) while T helper 1-like (CD4(+)IL-18R(+)) cells were more frequent in blood (p andlt; 0.001). The only significant differences between ACS and SA patients involved NK cells that were reduced in the ACS group. However, despite being reduced, the NK cell fraction in ACS patients contained a significantly higher proportion of IL-18R(+) cells compared with SA patients (p andlt; 0.05). less thanbrgreater than less thanbrgreater thanConclusion: There were several differences in lymphocyte subpopulations between blood and lymph nodes. However, the lymphocyte perturbations in peripheral blood of ACS patients compared with SA patients were not mirrored in lymph nodes. The findings indicate that lymph node analyses in multivessel coronary artery disease may not reveal any major changes in the immune response that are not detectable in blood.

Place, publisher, year, edition, pages
Public Library of Science, 2012
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-77542 (URN)10.1371/journal.pone.0032691 (DOI)000303005000033 ()
Note
Funding Agencies|Swedish Heart-Lung Foundation|20090489|Swedish Research Council|2008-2282|Available from: 2012-05-25 Created: 2012-05-22 Last updated: 2017-12-07
Bergström, I., Backteman, K., Lundberg, A., Ernerudh, J. & Jonasson, L. (2012). Persistent accumulation of interferon-gamma-producing CD8(+)CD56(+) T cells in blood from patients with coronary artery disease. Atherosclerosis, 224(2), 515-520
Open this publication in new window or tab >>Persistent accumulation of interferon-gamma-producing CD8(+)CD56(+) T cells in blood from patients with coronary artery disease
Show others...
2012 (English)In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 224, no 2, p. 515-520Article in journal (Refereed) Published
Abstract [en]

Objective: There is emerging evidence for CD8(+) T cell alterations in blood from patients with coronary artery disease (CAD). We examined whether the distribution and phenotype of CD8(+)CD56(+) T cells differed according to the clinical manifestation of CAD. less thanbrgreater than less thanbrgreater thanMethods: Patients with acute coronary syndrome (ACS, n = 30), stable angina (SA, n = 34) and controls (n = 36) were included. Blood was collected before and up to 12 months after referral for coronary investigation. CD8(+)CD56(+) T cells were assessed by flow cytometry for expression of surface markers, apoptosis, and intracellular expression of cytokines. less thanbrgreater than less thanbrgreater thanResults: The proportions of CD8(+)CD56(+) T cells were significantly higher in both ACS and SA patients compared with controls, and remained so after 3 and 12 months. This was independent of age, sex, systemic inflammation and cytomegalovirus seropositivity. CD8(+)CD56(+) T cells differed from CD8(+)CD56(-) T cells in terms of lower CD28 expression and fewer apoptotic cells. Both CD8(+) T cell subsets were positive for interferon (IFN)-gamma and tumor necrosis factor, although IFN-gamma was significantly more confined to the CD8(+)CD56(+) T cells. less thanbrgreater than less thanbrgreater thanConclusion: The persistent accumulation of CD8(+)CD56(+) T cells in ACS and SA patients share several features with immunological aging. It also contributes to a larger IFN-gamma(+) pool in blood, and may thereby hypothetically drive the atherosclerotic process in a less favorable direction.

Place, publisher, year, edition, pages
Elsevier, 2012
Keywords
Acute coronary syndrome, Coronary artery disease, Cytokines, Immune system, Leukocytes
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-84895 (URN)10.1016/j.atherosclerosis.2012.07.033 (DOI)000309261400039 ()
Note

Funding Agencies|Swedish Research Council||Swedish Heart-Lung Foundation||County Council of Ostergotland, Sweden||Eleanora Demeroutis Foundation, Linkoping, Sweden||Heart Foundation at Linkoping University, Linkoping, Sweden||

Available from: 2012-10-26 Created: 2012-10-26 Last updated: 2017-12-07
Bergström, I., Backteman, K., Ernerudh, J. & Jonasson, L. (2011). ACCUMULATION OF CD56+CD8+T CELLS IN PATIENTS WITH CORONARY ARTERY DISEASE: HIGH PRODUCTION OF IFN-GAMMA BUT DIFFERENTIAL EXPRESSION OF ANNEXIN 1 in INFLAMMATION RESEARCH, vol 60, issue , pp 223-223. In: INFLAMMATION RESEARCH (pp. 223-223). Springer Science Business Media, 60
Open this publication in new window or tab >>ACCUMULATION OF CD56+CD8+T CELLS IN PATIENTS WITH CORONARY ARTERY DISEASE: HIGH PRODUCTION OF IFN-GAMMA BUT DIFFERENTIAL EXPRESSION OF ANNEXIN 1 in INFLAMMATION RESEARCH, vol 60, issue , pp 223-223
2011 (English)In: INFLAMMATION RESEARCH, Springer Science Business Media , 2011, Vol. 60, p. 223-223Conference paper, Published paper (Refereed)
Abstract [en]

n/a

Place, publisher, year, edition, pages
Springer Science Business Media, 2011
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-69893 (URN)000291358900615 ()
Available from: 2011-08-09 Created: 2011-08-08 Last updated: 2011-08-09
Eriksson, P., Ernerudh, J., Nyström, S. A., Backteman, K. & Sardell, C. (2011). Increased plasma levels of CXCL1 and CCL20 reflecting Th17 activity in active WG and MPA in CLINICAL AND EXPERIMENTAL IMMUNOLOGY, vol 164, issue , pp 150-150. In: CLINICAL AND EXPERIMENTAL IMMUNOLOGY (pp. 150-150). Blackwell Publishing Ltd, 164
Open this publication in new window or tab >>Increased plasma levels of CXCL1 and CCL20 reflecting Th17 activity in active WG and MPA in CLINICAL AND EXPERIMENTAL IMMUNOLOGY, vol 164, issue , pp 150-150
Show others...
2011 (English)In: CLINICAL AND EXPERIMENTAL IMMUNOLOGY, Blackwell Publishing Ltd , 2011, Vol. 164, p. 150-150Conference paper, Published paper (Refereed)
Abstract [en]

n/a

Place, publisher, year, edition, pages
Blackwell Publishing Ltd, 2011
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-67839 (URN)000289409300229 ()
Available from: 2011-04-29 Created: 2011-04-29 Last updated: 2013-10-25
Backteman, K., Ernerudh, J. & Jonasson, L. (2011). LYMPHOCYTE SUBPOPULATIONS IN LYMPH NODES AND PERIPHERAL BLOOD. A COMPARISON BETWEEN PATIENTS WITH STABLE ANGINA AND ACUTE CORONARY SYNDROME in INFLAMMATION RESEARCH, vol 60, issue , pp 215-216. In: INFLAMMATION RESEARCH (pp. 215-216). Springer Science Business Media, 60
Open this publication in new window or tab >>LYMPHOCYTE SUBPOPULATIONS IN LYMPH NODES AND PERIPHERAL BLOOD. A COMPARISON BETWEEN PATIENTS WITH STABLE ANGINA AND ACUTE CORONARY SYNDROME in INFLAMMATION RESEARCH, vol 60, issue , pp 215-216
2011 (English)In: INFLAMMATION RESEARCH, Springer Science Business Media , 2011, Vol. 60, p. 215-216Conference paper, Published paper (Refereed)
Abstract [en]

n/a

Place, publisher, year, edition, pages
Springer Science Business Media, 2011
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-69892 (URN)000291358900593 ()
Available from: 2011-08-09 Created: 2011-08-08 Last updated: 2011-08-09
Eriksson, P., Sandell, C., Backteman, K. & Ernerudh, J. (2010). B Cell Abnormalities in Wegeners Granulomatosis and Microscopic Polyangiitis: Role of CD25+-expressing B Cells. JOURNAL OF RHEUMATOLOGY, 37(10), 2086-2095
Open this publication in new window or tab >>B Cell Abnormalities in Wegeners Granulomatosis and Microscopic Polyangiitis: Role of CD25+-expressing B Cells
2010 (English)In: JOURNAL OF RHEUMATOLOGY, ISSN 0315-162X, Vol. 37, no 10, p. 2086-2095Article in journal (Refereed) Published
Abstract [en]

Objective. The use of rituximab in vasculitis has increased interest in B cell biology. A subpopulalion of B cells expressing CD25 shows antigen-presenting properties and may have regulatory functions. We assessed subpopulations of B cell maturation (Bm) and markers related to activity and antigen presentation, and related the findings to disease activity. Methods. Multiparameter flow cytometry was used to assess numbers and proportions of circulating lymphocytes from 34 patients with vasculitis (16 remission, 18 active) and 20 controls. Results. Active vasculitis samples showed decreased proportions of Bm1 (7.8% vs 11%; p = 0.041), Bm2 (0.2% vs 0.7%; p = 0.002), and Bm3/Bm4 (0.1% vs 0.3%; p = 0.006), compared with controls; Bm2 cells were the most frequently occurring B cells but they were not significantly different in active vasculitis (74% vs 62%; p = 0.083). In patients with remission the proportion of CD25+ B cells was increased compared to controls (48% vs 29%, respectively; p = 0.006) and also compared to active vasculitis (23%; p = 0.006). The proportion of CD86+ B cells was also increased (31%) compared to active vasculitis (8%; p = 0.001), and to controls (6%; p = 0.0003). In multivariate analysis. Bm2 cells and CD25+27- B cells were independently influencing the patient group. Conclusion. In active vasculitis, a lower proportion of Bm I cells may indicate activated B cells. Patients in remission had higher proportions of CD25+ (a-chain of interleukin 2 receptor) and CD86+ (costimulatory molecule) B cells. We suggest that these B cells may have a regulatory role, or alternatively may result from previous treatment.

Place, publisher, year, edition, pages
Journal of Rheumatology, 2010
Keywords
VASCULITIS, ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES, B CELLS, CD25
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-60883 (URN)10.3899/jrheum.100074 (DOI)000282864400018 ()
Available from: 2010-10-29 Created: 2010-10-29 Last updated: 2013-10-25
Organisations

Search in DiVA

Show all publications