Patients with B cell chronic lymphocytic leukaemia have an expanded population of CD4+ perforin expressing T cells enriched for human cytomegalovirus specificity and an effector-memory phenotype

We have previously shown an expansion of cytotoxic antigen‐experienced CD4⁺T cells (CTLs) that express perforin (PF) in the peripheral blood of patients with B cell chronic lymphocytic leukaemia (B‐CLL). Increased frequencies of CD4⁺CTLs have since been attributed to chronic viral infections, particularly, human cytomegalovirus (HCMV). The present study examined the involvement of CD4⁺CTLs in responses to HCMV in B‐CLL, and characterized their differentiation. We studied 36 HCMV seropositive (SP) and seronegative B‐CLL patients and 20 healthy age‐matched individuals. The HCMV reactivity of CD4⁺PF⁺ and CD4⁺PF^? cells was determined by interferon‐gamma expression, and expression of CD45RA and CCR7 was assessed by flow cytometry. Fluorescence in‐situ hybridization was used to measure relative telomere lengths. CD4⁺PF⁺T cell expansion in B‐CLL patients and controls was strongly associated with HCMV seropositivity. CD4⁺PF⁺ compared to CD4⁺PF^? cells from SP B‐CLL patients elicited major histocompatibility complex (MHC) class II‐restricted responses to HCMV. CD4⁺PF⁺T cells from patients and controls were enriched with highly differentiated T‐effector/memory (CCR7^?) and revertant (CCR7^?CD45RA⁺) phenotype. CD4⁺PF⁺T cells from B‐CLL patients had shorter telomeres than CD4⁺PF^?T cells, indicating an extensive replicative history. We conclude that persistent exposure to HCMV antigens in SP B‐CLL patients leads to an expansion of the circulating MHC class II‐restricted CD4⁺PF⁺T cell population with effector/memory phenotype.     

Chimeric antigen receptor modified T cells that target chemokine receptor CCR4 as a therapeutic modality for T‐cell malignancies

With the emerging success of treating CD19 expressing B cell malignancies with ex vivo modified, autologous T cells that express CD19‐directed chimeric antigen receptors (CAR), there is intense interest in expanding this evolving technology to develop effective modalities to treat other malignancies including solid tumors. Exploiting this approach to develop a therapeutic modality for T cell malignancies for which the available regimens are neither curative, nor confer long term survival we generated a lentivirus‐based CAR gene transfer system to target the chemokine receptor CCR4 that is over‐expressed in a spectrum of T cell malignancies as well as in CD4⁺CD25⁺Foxp3⁺T regulatory cells that accumulate in the tumor microenvironment constituting a barrier against anti‐tumor immunity. Ex vivo modified, donor‐derived T cells that expressed CCR4 directed CAR displayed antigen‐dependent potent cytotoxicity against patient‐derived cell lines representing ATL, CTCL, ALCL and a subset of HDL. Furthermore, these CAR T cells also eradicated leukemia in a mouse xenograft model of ATL illustrating the potential utility of this modality in the treatment of a wide spectrum of T cell malignancies.     

Acquisition of t(11;14) in a patient with chronic lymphocytic leukemia carrying both t(14;19)(q32;q13.1) and +12

A rare recurrent chromosomal translocation, t(14;19)(q32;q13), has been identified in a variety of B‐cell malignancies, including chronic lymphocytic leukemia (CLL). We report a unique case of CLL in a patient carrying both trisomy 12 and t(14;19) (q32;q13.1), in whom t(11;14)(q13;q32) developed at relapse. The patient was a 77‐yr‐old woman, and her lymphoma cells at presentation showed CD5⁺, CD10^?, CD19⁺, CD20⁺(dim), CD23⁺, CD38⁺, and CD11c⁺. At relapse, the patient's lymphoma cells showed positive staining for cyclin D1 in addition to CD5, CD20, and CD23. Lymphoma cells in specimens at both presentation and relapse were positive for lymphoid enhancer factor 1 (LEF1) and negative for sex‐determining region Y‐box 11 (SOX11). IGH‐BCL1 FISH became positive at relapse. Split FISH assay using BCL1, BCL3, IGH, and CCND1 probes on lymph node specimens obtained at presentation and at autopsy confirmed that the translocation of BCL3 was solely detected in the lymph node at presentation and detected BCL3 and CCND1 translocations in the specimen at autopsy. These observations indicated that IGH‐BCL3 and IGH‐CCND1 had occurred in the same clone after treatment of the disease. In line with immunohistochemical and cytogenetic studies, additional PCR analysis of the FR3‐JH region showed the same sequence derived from IGHV4‐34 in specimens obtained at disease onset and relapse.     

Increased CD4(+) CD69(+) CD25(-) T cells in patients with hepatocellular carcinoma are associated with tumor progression

Background and Aim: A new subset of Treg cells, CD4⁺CD69⁺CD25^‐ T cells, has been identified in mice. Herein, we aimed to identify this subset of T cells and to evaluate its function in patients with hepatocellular carcinoma (HCC). Methods: We detected CD4⁺CD69⁺CD25^‐ T cells and its expression of CCR6 and transforming growth factor‐β1 (TGF‐β1) in peripheral blood of 91 HCC patients, 38 chronic hepatitis patients and 34 healthy donors by flow cytometry. CD4⁺CD69⁺CD25^‐ T cells in HCC tissues were also analyzed. Results: CD4⁺CD69⁺CD25^‐ T cells were significantly increased in peripheral blood of HCC patients compared with healthy persons and chronic hepatitis patients (8.74% ± 0.42% vs 4.55% ± 0.33% and 5.15% ± 0.36%, P < 0.0001). The percentage of peripheral CD4⁺CD69⁺CD25^‐ T cells was significantly higher in HCC patients with Tumor Node Metastasis (TNM) stage III plus IV (P < 0.05). Patients with large tumor size and tumor vascular invasion were inclined to obtain high percentage of CD4⁺CD69⁺CD25^‐ T cells (P < 0.05). The frequency of membrane‐bound TGF‐β1 positive cells in CD4⁺CD69⁺CD25^‐ T cells from HCC patients was higher than that from the other two groups (P < 0.0001). A considerable proportion of CD4⁺CD69⁺CD25^‐ T cells were present in HCC tissues, which has significant correlation with tumor size and TNM stage. Few CD4⁺CD69⁺CD25^‐ T cells express CCR6 both in peripheral blood and tumor tissues from HCC patients. Conclusions: Increased CD4⁺CD69⁺CD25^‐ T cells in HCC patients are significantly correlated with tumor size, vascular invasion and TNM stage. Thus, increased CD4⁺CD69⁺CD25^‐ T cells exert a critical role in HCC progression and might be a clinically aggressive phenotype of HCC.     

Increased frequency of CD4+PD-1+HLA-DR+ T cells is associated with disease progression in CLL

Chronic lymphocytic leukaemia (CLL) patients often have abnormal expansions of CD4⁺ and CD8⁺ T cells and this can be associated with progressive disease. To characterise the key T-cell populations involved in this phenomenon, we used flow cytometry and 11 phenotypic markers to study 74 CLL patients and 14 controls. T cells of CLL patients were more phenotypically complex than those of healthy controls with significant increases in the frequencies of CD4 and CD8 memory T cells expressing exhaustion-, activation- and senescence-associated markers. Multivariate analysis of 111 different T-cell subsets showed that high frequencies of four subsets (three CD8 and one CD4) were associated with shorter progression-free survival. The most significant association was with CD4⁺HLA-DR⁺PD-1⁺ T cells, and patients could be stratified into high- and low-risk groups based on the frequency of these T cells. The expansion of this CD4⁺ subset could not be accounted for by age, cytomegalovirus infection or increases in Treg cells. Overall, these results highlight two relatively simple biomarkers, percentage CD8⁺ and percentage CD4⁺PD-1⁺HLA-DR⁺ T cells, which can be used to risk-stratify CLL patients, independent of other tumour-associated markers. They also provide further evidence for the pivotal role of T cells in modulating the pathology of CLL.     

The clinical and biological features of a series of immunophenotypic variant of B‐CLL

Objectives: To describe the clinical and biological features of a series of immunophenotypic variant of B‐CLL (v‐CLL) characterised by intermediate RMH score, in the absence of t(11;14)(q13;q32) in FISH analysis in comparison with a series of typical CLL. Methods: We studied the clinical and biological features of 63 cases of v‐CLL and 130 cases of CLL. Results: We observed significant differences in terms of age <70 yr (P < 0.001), lymphocytosis <20 × 10⁹/L (P < 0.001), lymphocyte doubling time ≤12 months (P = 0.02), high serum β2‐microglobulin levels (P < 0.001) and splenomegaly (P = 0.002); CD38, CD49d, CD1c were more expressed in v‐CLL, CD43 in CLL (P < 0.001). IgV_H mutation and trisomy 12 were more frequent in v‐CLL group (P = 0.001; P < 0.001); del13q14 in CLL (P = 0.008). Gene expression profiling of nine v‐CLL and 60 CLL indicated that the atypical group presented a specific molecular pattern. After a median follow‐up of respectively, 55 (4–196) and 60 months (6–180), 25/42 patients with v‐CLL (48%) and 55/93 patients with CLL (59%) were treated. Time to treatment was significantly shorter in IgV_H‐mutated v‐CLL vs. mutated CLL (P = 0.006). The median overall survival was worse in v‐CLL‐mutated cases (P = 0.062). Conclusion: v‐CLL should be identified and dealt with separately from classic CLL. In particular, the prognostic markers that are routinely used to characterise classical B‐CLL should not be interpreted as having the same meaning.     

Functional expression of the eotaxin receptor CCR3 in CD30+ cutaneous T-cell lymphoma

Little is known about mechanisms involved in skin-specific homing of cutaneous T-cell lymphoma (CTCL). Chemokine/chemokine receptor interactions have been implicated in the homing of lymphoma cells to various tissue sites. We investigated tissue samples and tumor cell suspensions of patients with CD30(+) CTCL (n = 8) and CD30(-) CTCL (mycosis fungoides, n = 6; Sézary syndrome, n = 6) for expression of the chemokine receptors CCR3, CCR4, and CCR8 and the CCR3 ligands eotaxin/CCL11, monocyte chemoattractant protein 3 (MCP-3)/CCL7, and RANTES (regulated on activation, normal T expressed and secreted)/CCL5. Of 8 CD30(+) CTCLs, 7 expressed CCR3, 4 CCR4, and none CCR8. CCR3 expression was not found in skin tissue samples from 12 CD30(-) CTCLs. Coexpression of CCR3 and CD30 was demonstrated by flow cytometry in tumor cell suspensions. Internalization experiments demonstrated functionality of CCR3 expressed by freshly isolated tumor cells. Actin polymerization as well as migration in response to eotaxin was demonstrated in a CD30(+) cutaneous lymphoma cell line. CCR3 ligand eotaxin/CCL11 was detected in lesional skin of CD30(+) CTCL by immunohistochemistry, preferentially in tumor cells. Eotaxin/CCL11 expression in tumor cells was confirmed by intracellular immunofluorescence. Analysis of cytokine expression pattern of CCR3-bearing infiltrating cells showed a predominance of interleukin-4 (IL-4) but not interferon-gamma (IFN-gamma) protein expression,1 consistent with a T-helper 2 (Th-2) profile. These results suggest that expression of CCR3 and its ligand eotaxin/CCL11 plays a role in the recruitment and retention of CD30(+) malignant T cells to the skin.     

CD34(+)/CD38(-) stem cells in chronic myeloid leukemia express Siglec-3 (CD33) and are responsive to the CD33-targeting drug gemtuzumab/ozogamicin

Background

CD33 is a well-known stem cell target in acute myeloid leukemia. So far, however, little is known about expression of CD33 on leukemic stem cells in chronic leukemias.

Design and Methods

We analyzed expression of CD33 in leukemic progenitors in chronic myeloid leukemia by multi-color flow cytometry and quantitative polymerase chain reaction. In addition, the effects of a CD33-targeting drug, gemtuzumab/ozogamicin, were examined.

Results

As assessed by flow cytometry, stem cell-enriched CD34⁺/CD38⁻/CD123⁺ leukemic cells expressed significantly higher levels of CD33 compared to normal CD34⁺/CD38⁻ stem cells. Moreover, highly enriched leukemic CD34⁺/CD38⁻ cells (>98% purity) displayed higher levels of CD33 mRNA. In chronic phase patients, CD33 was found to be expressed invariably on most or all stem cells, whereas in accelerated or blast phase of the disease, the levels of CD33 on stem cells varied from donor to donor. The MDR1 antigen, supposedly involved in resistance against ozogamicin, was not detectable on leukemic CD34⁺/CD38⁻ cells. Correspondingly, gemtuzumab/ozogamicin produced growth inhibition in leukemic progenitor cells in all patients tested. The effects of gemtuzumab/ozogamicin were dose-dependent, occurred at low concentrations, and were accompanied by apoptosis in suspension culture. Moreover, the drug was found to inhibit growth of leukemic cells in a colony assay and long-term culture-initiating cell assay. Finally, gemtuzumab/ozogamicin was found to synergize with nilotinib and bosutinib in inducing growth inhibition in leukemic cells.

Conclusions

CD33 is expressed abundantly on immature CD34⁺/CD38⁻ stem cells and may serve as a stem cell target in chronic myeloid leukemia.     

Naïve subset develops the most important alloreactive response among human CD4+ T lymphocytes in Human Leukocyte Antigen‐identical related setting

In longitudinal clinical studies, receiving a high percentage of allogeneic donor‐derived CD4⁺CCR7⁺ T cells, which include naïve and central memory subsets have been correlated with increased incidence and severity of acute GVHD. Whether naïve and central memory CD4⁺ T‐cell subsets contribute more or equally to alloimmune responses are still unclear in human. The aim of this study was to investigate in vitro the alloreactive response of purified naïve, central memory, and effector memory CD4⁺ T‐cell subsets in HLA identical setting. By coculturing monocyte‐derived dendritic cells and purified CD4⁺ T‐cell subsets, from healthy HLA‐identical male and female sibling pairs, we found that naïve CD4⁺CCR7⁺CD45RA⁺ T cells developed the highest proliferative response upon stimulation by minor histocompatibility antigens and were progressively driven to produce high levels of interferon‐γ, tumor necrosis factor, and interleukin‐6. Comparatively, the central memory CD4⁺CCR7⁺CD45RA^neg subset proliferated to a lower extent and produced very low amounts of pro‐inflammatory cytokines while the CCR7^neg effector memory CD4⁺ subset was unresponsive. This study demonstrates the superior capacity of naïve CD4⁺ T cells to mount a primary alloreactive response as compared to central memory T cells. Their proliferative response associated with a pro‐inflammatory differentiation makes them potentially acute GVHD inducers. These in vitro results in line with what we have observed in clinical studies and may also lend support to approaches of partial selective T‐cell depletion for GVHD prevention.     

Association of circulating regulatory T cell number with the incidence and prognosis of diffuse large B‐cell lymphoma

Regulatory T (Treg) cells are essential for maintaining immune tolerance. High Treg frequencies have been reported in peripheral blood and tissue samples of patients with solid tumors while their role in lymphomas, including diffuse large B‐cell lymphoma (DLBCL) has not been clearly established. In this study, we analyzed the circulating Treg numbers in 27 patients with newly diagnosed DLBCL and 17 healthy individuals. Tregs were detected by flow cytometry based on CD4⁺CD25^highFoxP3⁺ phenotype. In addition, the expression of CD45RA, HLA‐DR, CD62L, CD39, and CTLA4 was analyzed. The number of circulating Treg cells was lower in patients with DLBCL than in healthy controls: median 23 (range, 4–107)/μL vs. 41 (19–104)/μL (P = 0.04). In particular, the number of Tregs expressing CD45RA (naïve Tregs), HLA‐DR (marker of activation), and CD62L (L‐selectin) was decreased in the DLBCL group. Lower (below median) number of circulating Tregs was associated with reduced chance of achieving complete remission (29% vs. 69%, P = 0.05) and reduced probability of even‐free survival (24% vs. 84% at 1 yr, P = 0.0004), independently on the International Prognostic Index. We conclude that low number of circulating Tregs may be associated with poor prognosis in patients with DLBCL. However, our observations require confirmation in larger patient population.     

Antigenic fractions of Leishmania (Viannia) braziliensis: the immune response characterization of patients at the initial phase of disease

American cutaneous leishmaniasis (ACL) has different clinical manifestations and these manifestations are dependent on the immunological status of the host. As CD4⁺ and CD8⁺ T cells and their mediators play a fundamental role in the host response to Leishmania and there is also a search for antigenic molecules to be used as future vaccines and tools for prognostic tests, this study characterized ACL patients’ immune response after stimulation with soluble and insoluble fractions of L. (V.) braziliensis. We demonstrated a prevailing production of the Th2 cytokines, IL‐4 and IL‐10 and a specific production of IFN‐γ and TNF‐α in patients before treatment. There was also a predominance of CD4⁺ T cells and a small percentage CD8⁺ T cells. The insoluble antigenic fraction primarily stimulated CD4⁺ T cells, while the soluble antigenic fraction showed a mixed profile, with CD4⁺ T cells being the main responsible for Th2 cytokines and CD8⁺ T cells for Th1 cytokines. Therefore, our results showed that a down‐modulation of the Th1 type of response occurs in the initial phase of L. braziliensis disease, being the antigenic fractions capable of stimulating a specific immune response.     

Immunohistochemical evidence of a cytokine and chemokine network in three patients with Erdheim‐Chester disease: Implications for pathogenesis

Objective

Erdheim‐Chester disease (ECD) is a rare form of non–Langerhans' cell histiocytosis (LCH) of unknown etiology, characterized by diffuse histiocyte infiltration of bones and soft tissue. The purpose of this study was to assess cell proliferation and expression of cytokines, chemokines, and chemokine receptors that may potentially be important in histiocyte accumulation in ECD lesions.

Methods

Biopsies were performed on 3 patients with ECD. The diagnosis of the disease was based on clinical signs including typical radiologic osteosclerosis, and on the detection of foamy CD68+,CD1a− non–Langerhans' cell histiocytes on histologic examination. The expression of the proliferation marker Ki‐67 as well as of selected chemokine/chemokine receptor pairs and cytokines was analyzed by immunohistochemistry.

Results

In all samples, Ki‐67 was undetectable in CD68+ histiocytes. Conversely, these cells expressed the chemokines CCL2 (monocyte chemotactic protein 1), CCL4/macrophage inflammatory protein 1β (MIP‐1β), CCL5/RANTES, CCL20/MIP‐3α, and CCL19/MIP‐3β, and their counter‐receptors CCR1, CCR2, CCR3, CCR5, CCR6, and CCR7. Moreover, ECD histiocytes expressed interferon‐γ–inducible 10‐kd protein (CXCL10), which is specifically induced by interferon‐γ, and interleukin‐6 and RANKL, which are both implicated in bone remodeling. Finally, all cases showed a Th1‐type lymphocyte infiltrate.

Conclusion

Our data indicate that, similar to LCH, ECD lesions are characterized by a complex cytokine and chemokine network, which may orchestrate histiocyte activation and accumulation through an autocrine loop and contribute to the pathogenesis of the disease.

     

T-lymphocytes expressing CC chemokine receptor-5 are increased in frail older adults

OBJECTIVES: To evaluate the frequencies of T‐lymphocytes expressing CC chemokine receptor‐5 (CCR5⁺ T‐cells) and their relationship with frailty in older adults. DESIGN: Case‐control study with an age‐, race‐, and sex‐matched design. SETTING: General Clinical Research Center. PARTICIPANTS: Community‐dwelling adults aged 72 and older from Baltimore, Maryland. METHODS: Frailty was determined using five validated criteria: weakness, slow walking speed, fatigue, low physical activity, and weight loss. Those meeting three or more of these five criteria were defined as frail and those with none as nonfrail. Complete blood counts were performed to obtain peripheral lymphocyte counts using an automated (Coulter) counter. Peripheral blood was collected for surface immunofluorescent staining of CCR5 and other T‐cell markers. RESULTS: Twenty‐six frail and matched nonfrail participants (mean age±standard deviation 83.8±5.3, range 72–94) completed the study. Frail participants had higher CCR5⁺, CCR5⁺CD8⁺, and CCR5⁺CD45RO^? T‐cell counts than matched nonfrail controls (349±160/mm³ vs 194±168/mm³, P=.02; 208±98/mm³ vs 105±62/mm³, P=.02; and 189±149/mm³ vs 52±36/mm³, P=.01; respectively). Furthermore, there was a trend toward graded increase in these T‐cell counts across the frailty scores in frail participants (e.g., CCR5⁺CD8⁺ counts of 123±52/mm³, 248±115/mm³, and 360±215/mm³ for those with frailty scores of 3, 4, and 5, respectively). CONCLUSION: These initial results suggest an expansion of the CCR5⁺ T‐cell subpopulation in frailty. They provide a basis for further characterization of CCR5⁺ T‐cells and their role in frailty, with potential therapeutic implications.     

CCR7 facilitates the pro‐inflammatory function of dendritic cells in experimental leishmaniasis

Cutaneous leishmaniasis, caused by the parasite Leishmania major, results in lesions at the site of infection, which are self‐healing in resistant hosts. However, in the absence of the chemokine receptor CCR7, mice are unable to heal the lesion and develop chronic disease. These B6.CCR7^?/? mice display an increased number of Th2 cells and immunosuppressive cytokine levels, as well as more regulatory T cells. As CCR7 is expressed on activated dendritic cells (DCs), and these cells require CCR7 to migrate to the draining lymph node, we expected decreased migration of DCs into the lymph node in the absence of CCR7 during cutaneous leishmaniasis. Consequently, in an attempt to initiate a self‐healing response, we adoptively transferred CCR7⁺ (B6.WT) DCs into the site of infection of B6.CCR7^?/? mice. Surprisingly, instead of healing the lesion, B6.CCR7^?/? mice inoculated with B6.WT DCs developed augmented lesions and showed increased immunosuppression compared to control B6.CCR7^?/? mice transferred with B6.CCR7^?/? DCs or B6.WT mice with B6.WT DCs. Finally, B6.WT mice injected with B6.CCR7^?/? DCs also presented delayed healing of the lesion. These results indicate that CCR7 must be expressed on DCs, as well as peripheral cells, to allow an efficient immune response to L. major.     

Signs of an in situ inflammatory reaction in scars of human American tegumentary leishmaniasis

Skin inflammation plays an important role during the healing of American tegumentary leishmaniasis (ATL), the distribution of cells in active lesions may vary according to disease outcome and parasite antigens in ATL scars have already been shown. We evaluated by immunohistochemistry, 18 patients with 1‐ or 3‐year‐old scars and the corresponding active lesions and compared them with healthy skin. Small cell clusters in scars organized as in the active lesions spreaded over the fibrotic tissue were detected, as well as close to vessels and cutaneous glands, despite a reduction in the inflammatory process. Analysis of 1‐year‐old scar tissue showed reduction of NOS2, E‐selectin, Ki67, Bcl‐2 and Fas expression. However, similar percentages of lymphocytes and macrophages were detected when compared to active lesions. Only 3‐year‐old scars showed reduction of CD3⁺, CD4⁺ and CD8⁺T cells, in addition to reduced expression of NOS2, E‐selectin, Ki67 and BCl‐2. These results suggest that the pattern of cellularity of the inflammatory reaction observed in active lesions changes slowly even after clinical healing. Analysis of 3‐year‐old scars showed reduction of the inflammatory reaction as demonstrated by decrease in inflammatory cells and in the expression of cell‐activity markers, suggesting that the host–parasite balance was only established after that period.     

Heterogeneity of T-Lymphocyte Chronic Lymphatic Leukaemia (CLL)

Lymphocyte surface markers (E-SRBC, EAC, EAγ and SmIg) and monoclonal antibodies (OKT3, OKT4, OKT8 and OKIa) were used to characterise the blood and bone marrow lymphocytes of T-cell CLL (8 patients). The diagnosis of T-cell CLL was made primarily as the majority of blood lymphocytes formed E-SRBC in ecah patient. Other markers – EAC, EAγ and SmIg – showed different patterns of association with E-SRBC. These findings considered together described 4 different phenotypes amongst these patients: (a) E⁺ (3 patients), (b) E⁺, EAC⁺ (1 patient), (c) E⁺, EAγ⁺ (2 patients), and (d) E⁺, SmIg⁺ (2 patients). Similarly, 4 different groups were defined with the help of monoclonal antibodies. Helper T-cell (3 patients) and suppressor T-cell (1 patient) CLL showed predominantly helper T- and suppressor T-lymphocytes respectively. Mixed T-cell CLL (1 patient) comprised an equal proportion of both subpopulations, while the remaining 3 patients, with excess of one or other subpopulations along with a considerable proportion of Ia antigen-bearing lymphocytes, formed the indeterminate cell type CLL.     

TARC expression in the circulation and cutaneous granulomas correlates with disease severity and indicates Th2-mediated progression in patients with sarcoidosis

Background

Sarcoidosis is a systemic disorder characterized by the accumulation of lymphocytes and monocyte/macrophage lineage cells that results in the formation of non-caseating granulomas. Thymus- and activation-regulated chemokine (TARC)/CCL17 is an important chemokine in the amplification of Th2 responses, which are achieved by recruiting CCR4-expressing CD4⁺ T lymphocytes. TARC concentrations are known to increase in the serum of sarcoidosis patients; however, its role in the assessment of severity and prognosis of sarcoidosis remains unknown. The objective of this study is to elucidate the role of TARC in sarcoidosis by investigating its expression in peripheral blood and at inflammatory sites. We also examined its relationship with clinical features.