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C O'Farrelly

Publications and source records attributed to C O'Farrelly.

At least 19 recordsLinked to original sources
PubMed2006

Smoking and thyroid-associated ophthalmopathy: A novel explanation of the biological link.

INTRODUCTION: Cigarette smoking is the strongest modifiable risk factor for developing thyroid-associated ophthalmopathy (TAO), and the severity of TAO is related to the current number of cigarettes smoked per day. We aimed to establish the effects of cigarette smoke extract (CSE) on an in vitro model of TAO. METHODS: Orbital tissue was taken during surgery from 10 patients with TAO and nine control subjects. Orbital fibroblasts were cultured and exposed to CSE, and intercellular adhesion molecule 1 (ICAM1) expression was measured by flow cytometry. Glycosaminoglycan production was measured by hyaluronic acid ELISA. Orbital fibroblasts were grown in adipogenic media with or without CSE and/or IL-1, and the degree of adipogenesis was quantified. RESULTS: Fibroblasts from patients with TAO and controls showed similar responses. ICAM1 expression was not affected by CSE. Hyaluronic acid production was stimulated by CSE in a dose-dependent manner (correlation coefficient, 0.978; P = 0.022), with 5% CSE causing an increase of 44% (P = 0.001). CSE increased adipogenesis in a dose-related manner, as did IL-1. The effects of CSE and IL-1 on adipogenesis were synergistic, with the degree of adipogenesis in the well containing both 5% CSE and 0.1 ng/ml IL-1 being double the magnitude of the sum of the values obtained from either stimulus alone (P < 0.001). Addition of an anti-IL-1 antibody to the well containing both 5% CSE and 0.1 ng/ml IL-1 reduced the degree of adipogenesis by 82% (P < 0.001). CONCLUSION: These findings may help explain how cigarette smoking has a detrimental effect in TAO and suggests that IL-1 may be an attractive therapeutic target in TAO.

Adipogenesis↗
PubMed2006

The effects of tumour necrosis factor-alpha and interleukin1 on an in vitro model of thyroid-associated ophthalmopathy; contrasting effects on adipogenesis.

OBJECTIVE: Cytokines are likely to play a key pathogenic role in thyroid-associated ophthalmopathy (TAO). Anti-cytokine therapy has been proposed to be a possible treatment for active TAO. We aimed to establish the effects of selected cytokines on intercellular adhesion molecule 1 (ICAM1) expression, glycosaminoglycan (GAG) production and adipogenesis in orbital fibroblasts (OFs) from patients with TAO. METHODS: Orbital tissue was taken during surgery from eight patients with TAO and five control subjects. OFs were cultured and ICAM1 expression measured by flow cytometry. GAG production was measured by hyaluronic acid ELISA. OFs were grown in adipogenic media and the degree of adipogenesis quantified. RESULTS: Responses were similar in OFs from patients with and without TAO. Tumour necrosis factor-alpha (TNFalpha) and interleukin1 (IL1) (0.1 ng/ml) stimulated ICAM1 expression by eight- to ten-fold. Anti-cytokine agents inhibited the cytokine-upregulated ICAM1 expression by 90-99% (P<0.01). TNFalpha and IL1 (0.1 ng/ml) increased hyaluronic acid production by 44 and 95% (P<0.01) respectively. Anti-cytokine agents inhibited these responses by 79-138% (P<0.04).0.013 AU and -1.0; P<0.03) whilst IL1 (0.1 ng/ml) stimulated adipogenesis (+0.05 AU and +5.7; P<0.02) measured by oil-red-O extraction and visual assessment respectively. The anti-IL1 agent inhibited IL1-mediated adipogenesis by 69-106% (P<0.04). CONCLUSION: TNFalpha and IL1 stimulate ICAM1 expression and GAG production, but have opposite effects on adipogenesis in OFs in vitro. IL1 promotes adipogenesis and its effects can be blocked by anti-IL1 agents in vitro. These agents may be the anti-cytokine treatment of choice for clinical trials in active TAO.

Adipogenesis↗
PubMed2005

Characterization of NKR+ T-cell subsets in human bone marrow: implications for immunosurveillance of neoplasia.

In addition to hematopoietic progenitors, human bone marrow contains mature T/NK lymphocytes. Valpha24Vbeta11 NKT-cells, a subset of NK receptor+ (NKR+) T-cells in humans, are rare in bone marrow, suggesting the presence of other NKR+ T-cells which may contribute to tumor surveillance. NKR+/- T-cells were examined in blood (PB), and bone marrow from donors (DM) and patients with active hematopoietic malignancy (PM), or in remission (PR). T-cells in PR & PM were enriched for CD56+ and CD57+ subsets, compared to DM. All marrow NKR+/- T-cell subsets were more activated than PB. PM and, surprisingly, PR marrow contained more activated cells than DM. CD8+ cells were significantly increased in all patient marrows and there was evidence of the formation of an effector/memory pool in malignant marrow. These data suggest that NKR+ T-cell enrichment in human bone marrow that has been exposed to neoplastic transformation is compatible with a role in localized tumor surveillance/eradication.

Biomarkers↗
PubMed2004

Hepatic interleuklin 15 (IL-15) expression: implications for local NK/NKT cell homeostasis and development.

Interleukin 15 (IL-15) is critical for the development of human and murine natural killer (NK) cells and hepatic-derived NK T cells (NKT) in mice, and for the homeostatic maintenance of NK/NKT and CD8(+) memory T cells. The lymphocyte repertoire of an adult human liver includes significant populations of NK and NKT-like cells, which may arise locally from hepatic haematopoietic stem cells (HSCs). We investigated hepatic IL-15 levels and the expression of IL-2/IL-15-receptor beta-chain (IL-2/IL-15Rbeta; CD122) on mature hepatic lymphocytes and HSCs. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect secreted/intracellular IL-15 transcripts. IL-15 protein was localized using immunohistochemistry; levels were measured by enzyme-linked immunosorbent assay IL-2/IL-15Rbeta expression by flow-cytometry. Normal hepatic IL-15 protein was detected at 0.43 ng/100 mg total protein (n = 11, range 0.10 ng-0.9 ng). There was a significant increase in HCV-infected tissue (1.78 ng, P < 0.005, n = 11, range 0.18-2.43 ng). The staining pattern suggests that infiltrating monocytes and tissue resident Kupffer cells are the main producers. IL-15 protein was detected in supernatants from cultured liver biopsy specimens in the absence of stimulation (mean 175.8 pg/100 mg wet tissue, n = 3), which increased significantly upon stimulation (P < 0.05, mean 231.21 pg). On average, 61% of hepatic HSCs expressed IL-2/IL-15Rbeta suggesting a local lymphopoietic role. Eighty per cent of NK and 45.8% of CD56(+) T cells expressed IL-2/IL-15Rbeta, suggesting involvement in local CD56(+) cell activation and expansion. Constitutive expression of IL-15 protein and IL-2/IL-15Rbeta on hepatic lymphocytes suggests a key role in the generation and maintenance of the unique hepatic lymphoid repertoire. The significant increase observed in HCV-infected liver suggests a role for IL-15 in host antiviral responses in the liver.

Adolescent↗
PubMed2003

A novel spectrofluorometric microassay for Streptococcus mutans adherence to hydroxylapatite.

Adherence to the tooth surface by Streptococcus mutans is an important step in initiation of dental caries. Current in vitro methods used to study bacterial adherence are time-consuming and may involve the use of radiolabels. The aim of this study was to develop a more convenient, high-throughput, microtitre-plate assay of bacterial adherence to hydroxylapatite. S. mutans was labelled with the fluorescent indicator BCECF/AM and fluorescence measured using a spectrofluorometer. Fluorescence microscopy confirmed label uptake. Optimal labelling occurred at 120 min with 50 microM BCECF/AM in DMSO. Viability was similar in control untreated bacterial cells, bacteria treated with DMSO alone or with the label for up to 4 h. Preliminary adherence experiments were performed using four commercially available types of hydroxylapatite. Fluorescence from pre-labelled bacteria was measured for bound cells. The assay was then optimised with respect to time and bacterial concentration using Fluka crude hydroxylapatite. Time course studies demonstrated that adherence reached saturation by 30 min incubation when using 1x10(7) cfu/ml labelled bacteria to 1 mg hydroxylapatite, coated with PBS or saliva. The fluorescence-based adherence assay was highly reproducible in repeated analyses and was useful in demonstrating interference with adherence. In conclusion, this microtitre-plate assay offers a more convenient approach to examine streptococcal adherence and could be used to screen for potential anti-adhesive agents.

Bacterial Adhesion↗
PubMed2003

Inherited thrombotic tendency in a pedigree with antithrombin La Rochelle (N405K) and factor V Leiden.

An Irish pedigree with a strong thrombotic tendency, due to the novel association of antithrombin La Rochelle (N405K) and factor V Leiden is described. Thromboses occurred at a median age of 16 years in four family members, carrying both mutant alleles. Molecular diagnosis was facilitated by the creation of an additional restriction enzyme site (Mnl1) in exon 6 of the antithrombin gene. Both the genes for antithrombin and factor V are located at chromosome 1q23. The molecular data and phenotypic behaviour in this family are strongly suggestive of allelic co-segregation of the mutant alleles.

Adolescent↗
PubMed2001

Selective expansion and partial activation of human NK cells and NK receptor-positive T cells by IL-2 and IL-15.

IL-2 and IL-15 are lymphocyte growth factors produced by different cell types with overlapping functions in immune responses. Both cytokines costimulate lymphocyte proliferation and activation, while IL-15 additionally promotes the development and survival of NK cells, NKT cells, and intraepithelial lymphocytes. We have investigated the effects of IL-2 and IL-15 on proliferation, cytotoxicity, and cytokine secretion by human PBMC subpopulations in vitro. Both cytokines selectively induced the proliferation of NK cells and CD56(+) T cells, but not CD56(-) lymphocytes. All NK and CD56(+) T cell subpopulations tested (CD4(+), CD8(+), CD4(-)CD8(-), alphabetaTCR(+), gammadeltaTCR(+), CD16(+), CD161(+), CD158a(+), CD158b(+), KIR3DL1(+), and CD94(+)) expanded in response to both cytokines, whereas all CD56(-) cell subpopulations did not. Therefore, previously reported IL-15-induced gammadelta and CD8(+) T cell expansions reflect proliferations of NK and CD56(+) T cells that most frequently express these phenotypes. IL-15 also expanded CD8alpha(+)beta(-) and Valpha24Vbeta11 TCR(+) T cells. Both cytokines stimulated cytotoxicity by NK and CD56(+) T cells against K562 targets, but not the production of IFN-gamma, TNF-alpha, IL-2, or IL-4. However, they augmented cytokine production in response to phorbol ester stimulation or CD3 cross-linking by inducing the proliferation of NK cells and CD56(+) T cells that produce these cytokines at greater frequencies than other T cells. These results indicate that IL-2 and IL-15 act at different stages of the immune response by expanding and partially activating NK receptor-positive lymphocytes, but, on their own, do not influence the Th1/Th2 balance of adaptive immune responses.

CD56 Antigen↗
PubMed2001

Expression of interleukin 7 (IL-7) mRNA and protein in the normal adult human liver: implications for extrathymic T cell development.

Interleukin-7 (IL-7) has been shown to play an essential role in T-cell development. Recombinase-activating gene (RAG)-1, RAG-2 and pre-TCR-alpha expression in the normal adult human liver (AHL), together with the presence of lymphoid-haematopoietic progenitors, is strong evidence that the AHL supports T cell maturation. We investigated IL-7 mRNA and protein levels in order to determine whether AHL could support T lymphocyte differentiation. Biopsies were snap frozen, powdered, and RNA/protein extracted. Reverse transcriptase polymerase chain reaction was used to detect IL-7 using primers that amplified 620 base pair (bp) fragments and other smaller transcripts. A sandwich enzyme-linked immunosorbent assay was developed to quantify IL-7 protein in homogenates. The anatomic distribution of IL-7-secreting cells was determined by immunohistochemistry. IL-7-specific product (620 bp) was detected in nine of ten samples, with six also positive for a smaller splice-variant (488 bp). Levels of the 620 bp product were 2.5 times greater than the 488 bp fragment. IL-7 protein was detected in all samples (range 18.47-76.93 pg/100 mg tissue). Immunohistochemistry demonstrated IL-7 protein in discrete cells of lymphoid morphology, widely distributed throughout the parenchyma and within portal tracts. Large populations of innate T cells are found in normal AHL, some of which may differentiate locally. The presence of IL-7 RNA and protein throughout normal hepatic tissue provides evidence that the normal AHL is a suitable microenvironment for T cell differentiation.

Adult↗
PubMed2001

Flow cytometric analysis of Clostridium difficile adherence to human intestinal epithelial cells.

Clostridium difficile is the most common cause of diarrhoea in hospitalised patients. Bacterial adherence to gut epithelial cells is a likely prerequisite to infection and toxin production. A novel flow cytometric method was developed for detecting adherence of C. difficile to human colonic and small intestinal epithelial cells (EC) and human intestinal cell lines. Small intestinal and colonic EC were isolated from biopsy specimens with mucolytic and chelating agents. Adherence of fluorochrome-labelled C. difficile to EC was measured by flow cytometry and was calculated as increase in median fluorescent intensity (deltaMFI). Cells with bacteria attached could be distinguished easily from cells alone or cells with unlabelled bacteria attached. Toxin-positive C. difficile adhered to colonic and small intestinal EC (deltaMFI mean 21.2 SD 16.7, n = 33 and 16.5 SD 20.7, n = 19 respectively). The toxin-negative strain also adhered to both epithelial cell types (deltaMFI 26.1 SD 32.5, n = 17 and 18.3 SD 31.3, n = 16). Adherence of toxin-positive C. difficile to the intestinal cell lines Caco-2 (deltaMFI 9.4 SD 4.4, n = 14) and HT29 (deltaMFI 8.1 SD 3.1, n = 12) was quantifiable, although at a significantly lower level than with primary colonic epithelial cells. Adherence of the toxin-negative strain was slightly lower, deltaMFI 6.5 SD 1.8, n = 9 with Caco-2 cells and deltaMFI 6.0 SD 2.0, n = 10 with HT29 cells. Adherence of C. difficile to epithelial cell lines was blocked with C. difficile antiserum, confirming specificity of adherence. In conclusion, flow cytometry is a useful approach to quantifying adherence of C. difficile to human colonic and small intestinal epithelial cells. Binding of toxin-negative as well as toxin-positive bacteria was detectable by this approach. Analysis of C. difficile adherence to target cells may have important implications for the understanding of the pathogenesis of C. difficile-related disease.

Bacterial Adhesion↗
PubMed2000

Isolation of lymphocytes from normal adult human liver suitable for phenotypic and functional characterization.

Murine and human studies have demonstrated that the normal liver contains significant numbers of resident lymphocytes that have functions distinct from those found in blood and other organs. To characterize these cells requires the isolation of viable lymphocytes that can be analysed by flow cytometry and in functional assays. The techniques classically used to isolate single cell suspensions of hepatic lymphocytes for phenotypic and functional studies involve mechanical and/or enzymatic dissociation of liver tissue. The aim of this study was to determine the effect of these procedures on surface molecule expression and lymphocyte function and to optimise an isolation technique that minimises these effects. Mechanical homogenisation of liver tissue alone resulted in low viable lymphocyte yields but these were improved by the combined use of mechanical and enzymatic techniques. A mean yield of 2.3 x 10(6) lymphocytes with a mean viability was 88.8% was obtained from 200 mg wedge biopsy samples of normal adult human liver using a combination of gentle mechanical dissociation followed by digestion with collagenase type IV and DNase I. These cells were suitable for phenotypic characterisation by flow cytometry. They also retained their ability to grow in vitro, to respond to cytokines and activation stimuli, to mediate cytotoxic killing of target cells, and to produce inflammatory and regulatory cytokines.

Adenosine↗
PubMed2000

Expansion of peripheral blood CD5+ B cells is associated with mild disease in chronic hepatitis C virus infection.

BACKGROUND/AIMS: Hepatitis C virus (HCV) infection is associated with the development of chronic liver disease and extra-hepatic manifestations, which include autoantibody production, immune-mediated diseases such as cryoglobulinaemia and B-cell lymphoproliferation. Recent identification of intra-hepatic clonal B cells capable of rheumatoid factor production, selective infection of B cells over T cells and of an HCV receptor on B lymphocytes strongly supports a central role for these cells in the immune response to HCV infection. In particular, CD5+ B cells which are capable of producing natural antibodies with autoreactive specificities are likely to be important in the development of HCV-associated autoimmunity and lymphoproliferation. METHODS: We have investigated the presence of CD5+ B cells in a unique cohort of HCV-infected women who were infected with a single inoculum of HCV genotype 1b following immunisation with contaminated anti-D immunoglobulin in 1977. RESULTS: CD5+ B cells are significantly increased in chronic HCV infection (37.66+/-1.92%) as compared with those with resolved infection (25.33+/-1.90%). High levels of CD5+ B cells were associated with the production of rheumatoid factor. The number of peripheral blood CD5+ B cells correlated negatively with histological activity index. CONCLUSIONS: The expansion of this B cell population in patients with active HCV infection may give rise to immune-mediated sequelae associated with HCV infection. This expanded population of CD5+ B cells may protect against the development of progressive liver disease.

Adult↗
PubMed2000

Innate and adaptive lymphoid cells in the human liver.

Because of its location and function, the liver is continuously exposed to a large antigenic load that includes pathogens, toxins, tumor cells and harmless dietary antigens. The range of local immune mechanisms required to cope with this diverse immunological challenge is now being appreciated. The liver has an "epithelial constitution" and contains large numbers of phagocytic cells, antigen-presenting cells and lymphocytes and is a site for the production of cytokines, complement components and acute phase proteins. In this review, we focus on the hepatic lymphoid system, which is currently emerging as an important arm of the immune system in the liver for targeting pathogens as well as for the recognition of cells that are modified as a result of infection or tumor transformation. We show that this organ contains a heterogeneity of lymphoid cells with diverse recognition mechanisms and functions. There are conventional T lymphocytes that use clonotypic receptors to identify and respond to antigenic peptides presented in the context of polymorphic class I and class II major histocompatibilty complex (MHC) molecules. But these cells are outnumbered by lymphoid cells that recognize common structures using receptors with limited diversity. These mediators of innate immunity against infectious pathogens and malignant cells respond immediately to stimuli and function as a temporal (and perhaps evolutionary) bridge for the adaptive immune response.

Acute-Phase Proteins↗
PubMed2000

Differential expression of lymphoid and myeloid markers on differentiating hematopoietic stem cells in normal and tumor-bearing adult human liver.

The presence and phenotype of lineage-committed hematopoietic progenitors in the normal adult human liver (AHL) were investigated and compared with the profiles of differentiating hematopoietic precursor populations detected in liver bearing metastases of colonic origin. Levels of hematopoietic stem cells (HSCs) (CD34(+)CD45(+)) detected in hepatic mononuclear cell (HMNC) populations were increased 6-fold when compared with matched peripheral blood samples. In normal liver, less than 5% of HSCs expressed the myeloid-associated antigen, CD33, whereas considerable proportions expressed lymphoid-associated markers (T cell, 33.39%; B cell, 17.39%; and natural killer [NK] cell, 37.17%). Significant increases were observed in the relative proportions of hepatic HSCs coexpressing CD33 (20.53%; P =.001), and the T-cell marker (CD7, 58. 13%; P =.02) in tumor-bearing liver compared with normal liver. HSCs with B-cell progenitor phenotype (CD19(+)) were significantly decreased in tumor-bearing liver (0.06%; P =.02). Despite these differences, the activation status of hematopoiesis, as measured by the coexpression of the differentiation and activation markers, CD38 and CD45RA, did not differ significantly between normal and tumor-bearing liver. These results indicate that the normal AHL harbors lineage-committed hematopoietic progenitors, and the vast majority of these progenitors express lymphoid-associated antigens with changes occurring in both the myeloid and lymphoid compartments of the hepatic hematopoietic pathway on tumor challenge. While tumor-bearing livers are enriched for intrahepatic myeloid precursors and T-cell progenitor cells, further studies are required to establish the origin and in situ development potential of hepatic HSCs in the adult human and their role in tumor immunity.

Adolescent↗
PubMed2000

Serum haptoglobin: an objective indicator of experimentally-induced Salmonella infection in calves.

Experimental models of Salmonella -induced gastroenteritis have previously relied on crude subjective clinical markers of infection to assess disease severity. The aim of this study was to investigate the possibility that changes in serum levels of the acute phase protein, haptoglobin, may be used as an objective, quantitative measurement of infection. Eight 3- to 4-week-old animals were challenged with a mixture of three Salmonella serotypes containing 6 x 10(10)bacteria and compared with five animals given a placebo preparation. Animals were monitored and characteristic clinical symptoms of infection; diarrhoeal scores, morbidity scores and rectal temperature, were recorded. Serum samples, from both animal groups, taken prior to challenge and again on days 1, 3, and 5 post-challenge, were analysed for haptoglobin levels using a direct serum binding assay. Prior to challenge, all 13 animals had normal levels of haptoglobin in their serum. By day 3 post-challenge six of eight animals challenged with Salmonella had abnormal serum haptoglobin levels (median level = 212 microg ml(-1)), while haptoglobin levels remained normal in placebo-challenged animals (median level = 0 microg ml(-1)). The change in haptoglobin levels during the 5-day observation period was statistically significant in the Salmonella -challenged animals (P = 0.0003, H = 16.477). Serum haptoglobin levels showed a statistical correlation with clinical measures of disease severity; diarrhoeal scores (P = 0.0015, H =8. 988), morbidity scores (P = 0.0004, H = 15.711) and rectal temperature (P = 0.0001, Z = 4.304). Thus, serum haptoglobin levels closely reflect the clinical symptoms of infection and are therefore a useful marker of infection severity in salmonellosis in calves.

Animals↗
PubMed2000

Menstrual cycle dependent fluctuations in NK and T-lymphocyte subsets from non-pregnant human endometrium.

PROBLEM: To establish the relative proportions of endometrial lymphocyte subpopulations during the menstrual cycle. METHOD OF STUDY: Lymphocytes were investigated by flow cytometry, during the early proliferative (EP), late proliferative (LP), early secretory (ES) and late secretory (LS) phases of the menstrual cycle. RESULTS: Between the LP and LS phases, there was an increase in NK cells from 26.4% to 83.2% (P = 0.0017) of the CD45+ population. T cells decreased from 55.06% to 6.7% (P = 0.0017). Within the T-cell population, CD8+ cells decreased significantly from 63.0% in the LP phase to 54.2% in the LS phase (P = 0.04). In contrast, potential regulatory populations such as double negative (DN) T cells CD3+CD4-CD8- and natural T cells (NT) CD3+CD56+, increased significantly in the LS phase (P = 0.05; P = 0.03). gammadelta T cells, predominantly of the DN and NT phenotypes remained consistently low at all stages of the cycle (2.34%). CONCLUSION: Endometrial lymphocyte fluctuations during the menstrual cycle may reflect hormonal regulation of maternal immunity, thereby promoting tolerance at the time of implantation.

Adult↗
PubMed2000

Is villous atrophy always and only the result of gluten sensitive disease of the intestine?

'Flat and flexible truths are beat out by every hammer' (Sir Thomas Browne, writer and physician) The prevalence of gluten-sensitive enteropathy (GSE) or coeliac disease is likely to be as high as 1:200 to 1:400 in the developed world. Current medical practice leaves a significant proportion of these cases undiagnosed. An association between untreated coeliac disease and intestinal malignancy is well described so it is possible that patients with undiagnosed coeliac disease constitute a significant reservoir of preventable gastrointestinal malignancy. However, it is not clear whether all patients with coeliac disease are equally at risk of malignancy nor are all cases of intestinal malignancy necessarily associated with wheat protein sensitivity. Thus the precise links between GSE, villous atrophy and malignancy have not yet been established. However, there is evidence that products of activated T-cell clones, be they antigen specific or malignant, influence epithelial cell proliferation, differentiation and function thus contributing to the histological lesion characteristic of GSE or small bowel lymphoma.

Animals↗
PubMed1999

The human liver contains multiple populations of NK cells, T cells, and CD3+CD56+ natural T cells with distinct cytotoxic activities and Th1, Th2, and Th0 cytokine secretion patterns.

The human liver contains significant numbers of T cells, NK cells, and lymphocytes that coexpress T and NK cell receptors. To evaluate their functional activities, we have compared the cytotoxic activities and cytokines produced by normal adult hepatic CD3+CD56- (T) cells, CD3-CD56+ (NK) cells, and CD3+CD56+ (natural T (NT)) cells. In cytotoxicity assays using immunomagnetic bead-purified NK cell, T cell, and NT cell subpopulations as effectors, fresh hepatic NK cells lysed K562 targets, while NT cells could be induced to do so by culturing with IL-2. Both NT and T cells were capable of redirected cytolysis of P815 cells using Abs to CD3. Flow cytometric analysis of cytokine production by fresh hepatic lymphocyte subsets activated by CD3 cross-linking or PMA and ionomycin stimulation indicated that NT cells and T cells could produce IFN-gamma, TNF-alpha, IL-2, and/or IL-4, but little or no IL-5, while NK cells produced IFN-gamma and/or TNF-alpha only. The majority of NT cells produced inflammatory (Th1) cytokines only; however, approximately 6% of all hepatic T cells, which included 5% of Valpha24 TCR-bearing NT cells and 2% of gammadeltaTCR+ cells, simultaneously produced IFN-gamma and IL-4. The existence of such large numbers of cytotoxic lymphocytes with multiple effector functions suggests that the liver is an important site of innate immune responses, early regulation of adaptive immunity, and possibly peripheral deletion of autologous cells.

Adult↗