Lymphocyte Subpopulations in Lymph Nodes and Peripheral Blood: A Comparison between Patients with Stable Angina and Acute Coronary Syndrome

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.Funding Agencies|Swedish Heart-Lung Foundation|20090489|Swedish Research Council|2008-2282

The CD14+CD16+ monocytes in erysipelas are expandend and show reduced cytokine production.

In human peripheral blood the classical CD14++DR+ monocytes and the pro-inflammatory CD14+CD16+DR++ monocytes can be distinguished. In erysipelas we found strongly increased numbers of CD14+CD16+ monocytes on the day of diagnosis (day 1) in 11 patients with an average of 150.5±76.0 cells/μl, while 1 patient had low levels (35 cells/μl, control donors 48.8±19.8 cells/μl). The classical monocytes were only moderately elevated in the erysipelas patients (factor 1.7 as compared to controls). Patients exhibited increased body temperature, erythrocyte sedimentation rate and increased serum levels for C-reactive protein (CRP), IL-6 and macrophage-colony-stimulating factor. Among these, body temperature and CRP showed a significant correlation to the numbers of CD14+CD16+ monocytes. In 4 of 4 patients with high levels of CD14+CD16+ monocytes, these levels returned to that seen in controls by day 5 of antibiotic therapy. Determination of intracellular TNF was performed by three-color immunofluorescence and flow cytometry after ex vivo stimulation withlipoteichoic acid, a typical constituent of streptococci. Here, patient CD14+DR++ pro-inflammatory monocytes showed a twofold lower level of intracellular TNF. By contrast, expression of TNF was unaltered in the classical CD14++ monocytes. These data show that in erysipelas the pro-inflammatory CD14+CD16+DR++ monocytes are substantially expanded and selectively tolerant to stimulation by streptococcal products. &nbsp

Differential CD4+ T-cell memory responses induced by two subsets of human monocyte-derived dendritic cells

Dendritic cells (DC) are powerful inducers of primary T-cell responses, but their role in secondary responses has not been extensively analysed. Here, we address the role of two DC subsets derived from human CD16+ (16+ mDC) or CD16– (16– mDC) monocytes on the reactivation of memory responses. CD4+ CD45RA– memory T cells were obtained from adult blood donors, and central (TCM) and effector (TEM) memory T cells were isolated by fluorescence-activated cell sorting with anti-CCR7 antibodies. The 16+ mDC and 16– mDC were cocultured with autologous lymphocytes, either unpulsed or loaded with purified protein derivatives of Mycobacterium tuberculosis (PPD) or tetanus toxoid (TT), and were analysed for up to 8 days. Over a range of doses, 16+ mDC drove stronger T-cell proliferative responses against both antigens. Overall, antigen-specific memory cells tended to acquire a phenotype of TEM at later time-points in the culture, whereas cells that had completed fewer cycles of division were similar to TCM. The 16+ mDC induced higher rates of proliferation on both TCM and TEM lymphocytes than 16– mDC. This phenomenon was not related to the ability of both DC to induce CD25 expression on T cells, to lower secretion of interleukin-2, or to raise production of interleukin-10 during T-cell/16– mDC cocultures. The induction of TCM effector capacity in terms of interferon-γ production was faster and more pronounced with 16+ mDC, whereas both DC had similar abilities with TEM. In conclusion, these data might reveal new potentials in vaccination protocols with 16+ mDC aimed at inducing strong responses on central memory T cells