Presence Of Monocytes Research Articles

Bovine viral diarrhoea virus induces apoptosis in blood mononuclear cells by a mechanism largely dependent on monocytes.

The induction of apoptosis by bovine viral diarrhoea virus (BVDV) was examined in bovine peripheral blood mononuclear cells (PBMC) incubated with an antigenically homologous pair of non-cytopathic and cytopathic BVDV. Our results show that the cytopathic biotype, in contrast to the non-cytopathic counterpart, induces apoptosis in PBMC. Flow cytometry analysis of cells undergoing apoptosis revealed that: (1) monocytes constitute the major cell population undergoing apoptosis; (2) cytopathic virus also induces apoptosis in BoCD4+, BoCD8+ and BoWC1+ T cells in whole PBMC cultures but not in purified T cell suspensions; (3) the degree of apoptosis of BoCD4+ and BoCD8+ T cells incubated with the cytopathic virus was significantly enhanced by the presence of monocytes. Taken together, these results suggest that bovine monocytes play an important role in apoptosis induced by cytopathic BVDV.

EFFECTS OF ANTI-CD2 MONOCLONAL ANTIBODY : CD2 AND CD95-MEDIATED APOPTOSIS OF HUMAN PERIPHERAL T CELLS.

380 The range of immunosuppressive agents developped in recent years for the therapy of organ allograft rejection includes anti-CD2 monoclonal antibody(mAb) that exert the apoptotic death of large activated T lymphocytes. We examined the relationship between proliferation and susceptibility to Fas- and CD2-mediated apoptosis of human peripheral T lymphocytes that had been exposed in primary culture to CD3- or CD2-derived mitogenic stimuli in the presence of monocytes and exogenous IL-2. After 5 days, activated T cells were fractionated into large (F2) and small (F6) cells on Percoll density gradients and analyzed for their susceptibility to apoptosis and for their position in the cell cycle. Most F6 cells displayed a CD45RA+, CD25-, CD2R- phenotype and were unable to incorporate bromodeoxyuridine (BrdUrd) during the entire culture period. However, they were activated to express Fas Ag and some cell cycle regulatory proteins specific to late G1 phase. T cells with proliferative unresponsiveness were sensitive to Fas-mediated apoptosis whether it was triggered by anti-Fas mAb or by Fas ligand, but were almost completely resistant to CD2 apoptotic signaling. In contrast, F2 cells exhibited classical activation markers (CD45RO, CD25 and CD2R) had crossed S phase at least once, and were sensitive to both Fas and CD2 apoptotic signals. In large cells harvested earlier (on day 3), the signals were operative in both BrdUrd+ and BrdUrd- cells. Thus, S phase entry is not required for Fas- and CD2-mediated apoptosis. The profound proliferative unresponsiveness of F6 cells to CD3 and CD2 stimuli (bypassed by ionomycin plus PMA) and the CD2R- conformation of their CD2 molecules suggest that they may be in vivo anergized cells whose elimination, upon restimulation, is highly dependent on the Fas death pathway.

Pattern of cytokine expression in circulation CD57 + T cells from long-term renal allograft recipients

We made a quantitative analysis of the lymphokine mRNA and of proteins produced by CD57 + and CD57 − circulating T cells isolated from long-term kidney-transplanted patients with expanded CD4 +/CD57 + and CD8 +/CD57 + T cells, and from normal individuals. We concentrated on IL-2 and IFN-γ, which define a Th1-like type of lymphokine production, and on IL-4 which defines a Th-2-like type. We also analysed the production of IL-10 which is endowed with inhibitory effects on IL-2 and IFN-γ-synthesis, and of TNF-α, a pleiotropic inflammatory cytokine. On ionomycin + PMA stimulation, which reveals the intrinsic potential of lymphokine production by T cells, the CD57 + T cell subsets from all individuals produced high amounts of IFN-γ and TNF-α mRNA and protein. They also produced IL-2, but to a much lesser extend than their CD57 − counterparts, and little IL-4 and IL-10. They were no more capable of producing IL-2 when stimulated through the CD3/TCR in the presence of monocytes, yet still synthesized IFN-γ. Our data suggest that the in vivo expansion of CD57 + T cells in stable allograft renal recipients might correspond to Th1 energized cells which on triggering of cell surface receptors hardly secrete lymphokines involved in cell cycle progression, but can still exert some effector functions, including IFN-γ secretion.

Monocyte-vascular smooth muscle cell interaction enhances nitric oxide production.

The adhesive interaction of monocytes and vascular smooth muscle cells (VSMCs) has been suggested to be a regulatory signal in the cellular activation that is involved in the pathogenesis of atherosclerosis. We investigated the effects of monocyte-VSMC interaction on inducible nitric oxide (NO) synthase expression. NO production by the cultured cells was determined by measuring the nitrite content of the culture media using the Griess reagent. The expression of inducible NO synthase protein was assayed by Western blotting. Interleukin-1 beta (IL-1 beta) induced nitrite production by VSMCs in a time-dependent manner. The addition of the mouse monocyte cell line J774 to IL-1 beta-stimulated VSMCs further increased nitrite production in a monocyte number-dependent manner. Enhanced nitrite production by coculture was accompanied by increased inducible NO synthase protein accumulation. Addition of tumor necrosis factor-alpha (TNF-alpha) also enhanced IL-1 beta-induced nitrite production by VSMCs, but TNF-alpha showed no effect in the presence of monocytes. Coculture of monocytes and VSMCs in the presence of IL-1 beta secreted substantial amounts of TNF-alpha. The production of nitrite by coculture was markedly inhibited by an anti-TNF-alpha antibody. The present study revealed that direct cell-to-cell interaction between monocytes and VSMCs enhances NO production, suggesting an important role for their interaction in the pathogenesis of atherosclerosis.

Relationship between proliferation and susceptibility to CD95- and CD2-mediated apoptosis in stimulated primary T lymphocytes: T cells manifesting proliferative unresponsiveness are preferentially susceptible to CD95-mediated apoptosis.

Abstract We examined the relationship between proliferation and susceptibility to Fas- and CD2-mediated apoptosis of human peripheral T lymphocytes that had been exposed in primary culture to CD3- or CD2-derived mitogenic stimuli in the presence of monocytes and exogenous IL-2. After 5 days, activated T cells were fractionated into large (F2) and small (F6) cells on Percoll density gradients and analyzed for their susceptibility to apoptosis and for their position in the cell cycle. Most F6 cells displayed a CD45RA+, CD25-, CD2R- phenotype and were unable to incorporate bromodeoxyuridine (BrdUrd) during the entire culture period. However, they were activated to express Fas Ag and some cell cycle regulatory proteins specific to late G1 phase. T cells with proliferative unresponsiveness were sensitive to Fas-mediated apoptosis whether it was triggered by anti-Fas mAb or by Fas ligand, but were almost completely resistant to CD2 apoptotic signaling. In contrast, F2 cells exhibited classical activation markers (CD45RO, CD25, and CD2R), had crossed S phase at least once, and were sensitive to both Fas and CD2 apoptotic signals. In large cells harvested earlier (on day 3), the signals were operative in both BrdUrd+ and BrdUrd- cells. Thus, S phase entry is not required for Fas- and CD2-mediated apoptosis. The profound proliferative unresponsiveness of F6 cells to CD3 and CD2 stimuli (bypassed by ionomycin plus PMA) and the CD2R- conformation of their CD2 molecules suggest that they may be in vivo anergized cells whose elimination, upon restimulation, is highly dependent on the Fas death pathway.

Ethanol and Natural Killer Cells. I. Activity and Immunophenotype in Alcoholic Humans

The human lymphocyte fraction with the greatest fresh killing activity against K562 targets is phenotypically the CD3−CD19−CD56+ subset There have been reports of reduced natural killer (NK) activity in human alcoholics, but overall consistency is lacking and phenotypic monitoring has been inadequate to allow reliable estimates of changes in the active cell fractions. We have evaluated a range of cell surface markers and fresh NK activity in controls and alcoholics, and now report abnormalities in both phenotype and function in some alcoholics, but a normal profile in others. Patients without evidence of active liver disease (AWLDs) tend to have normal fresh basal activities and phenotypic profiles. Patients with alcoholic liver disease (ALDs) have fewer Lin− lymphocytes that are CD56+. Three of 14 ALDs assayed in the present work had absent NK activity, whereas others were activated. In normal controls and in AWLDs, the presence of monocytes in the lytic assay consistently inhibits lysis; but, in some patients with ALD, the presence of monocytes is stimulatoty to NK activity. In alcoholics as one group, there is a statistically significant dative increase in a novel Lin− subset of unknown function; this subset has a phenotype of Lin−CD56−CD45RO+.

Ethanol and Natural Killer Cells. I. Activity and Immunophenotype in Alcoholic Humans

The human lymphocyte fraction with the greatest fresh killing activity against K562 targets is phenotypically the CD3-CD19-CD56+ subset. There have been reports of reduced natural killer (NK) activity in human alcoholics, but overall consistency is lacking and phenotypic monitoring has been inadequate to allow reliable estimates of changes in the active cell fractions. We have evaluated a range of cell surface markers and fresh NK activity in controls and alcoholics, and now report abnormalities in both phenotype and function in some alcoholics, but a normal profile in others. Patients without evidence of active liver disease (AWLDs) tend to have normal fresh basal activities and phenotypic profiles. Patients with alcoholic liver disease (ALDs) have fewer Lin- lymphocytes that are CD56+. Three of 14 ALDs assayed in the present work had absent NK activity, whereas others were activated. In normal controls and in AWLDs, the presence of monocytes in the lytic assay consistently inhibits lysis; but, in some patients with ALD, the presence of monocytes is stimulatory to NK activity. In alcoholics as one group, there is a statistically significant relative increase in a novel Lin- subset of unknown function; this subset has a phenotype of Lin-CD56-CD45RO+.

Endotoxin Activates T Cell Interferon-γ Secretion in the Presence of Endothelium

T lymphocytes (T cells) and their secreted lymphokine interferon-γ (IFN-γ) play important mediator roles in endotoxin-induced inflammation. We sought to explore the necessary conditions for and degree of LPS-induced T cell activation for IFN-γ secretion in a human syngeneic microvascular endothelial-T cell coculture system. Human peripheral blood T cells, with or without monocytes, were cocultured in the presence or absence of a syngeneic human adipose microvascular endothelial cell (HAMVEC) monolayer. Cocultures were stimulated with LPS (1 μg/ml) and 3-day coculture supernatants assayed for IFN-γ and IL-2 by ELISA. In the absence of HAMVEC, LPS-induced T cell activation for IFN-γ secretion was only minimally demonstrated in the presence of monocytes. However, in the presence of HAMVEC, LPS activated T cells for IFN-γ secretion in the absence of monocytes and markedly augmented the response in the presence of monocytes. A subset of donor cocultures showed no IFN-γ response to LPS. IL-2 was not secreted as part of the LPS-induced T cell activation response. Our data support a hypothesis that endothelium serves as an accessory cell for T cell IFN-γ secretion in endotoxin-induced inflammation. T cell-endothelial interactions may play a crucial role in promoting T cell activation during LPS-induced inflammation.

Modulation of WC1, a lineage-specific cell surface molecule of gamma/delta T cells augments cellular proliferation.

WC1, also known as T19, is the only unique gamma/delta T-cell differentiation antigen described to date other than the gamma/delta T-cell receptor. We present evidence that modulation of WC1 results in augmented proliferation of gamma/delta T cells. Immobilized IL-A29, a monoclonal antibody (mAb) specific for WC1, augmented proliferation of gamma/delta T cells in the autologous mixed leucocyte reaction (AMLR) as well as proliferation induced by either anti-CD3 or anti-CD5 mAb. In contrast, anti-CD5 mAb did not increase proliferation in the AMLR even though both CD5 and WC1 are members of the scavenger receptor cysteine-rich family of proteins and are expressed by bovine peripheral blood gamma/delta T cells. IL-A29 did not induce proliferation when assessed alone or in the presence of either phorbol myristate acetate (PMA) or interleukin-2. IL-A29 also did not induce detectable calcium mobilization when evaluated in the presence of monocytes, PMA, or following cross-linking of IL-A29 with anti-immunoglobulin antibody. We conclude that WC1 is a gamma/delta T-cell lineage-specific cell-surface differentiation antigen which is involved in activation of gamma/delta T cells using an as yet unidentified pathway.

Decreased production of IFNγ and increased production of IL‐6 by cord blood mononuclear cells of newborns with a high risk of allergy

The underlying mechanisms of elevated IgE level in atopic patients are still obscure, however, extensive efforts have been tried to identify an immunological parameter as a predictor of atopy. This study compared the difference in cytokine production by cord blood mononuclear cells between new borns with high-risk of allergy (family allergy score, FAS > or = 3) and those with low-risk (FAS = 0). Following stimulation with PHA (100 micrograms/mL) and PMA (1 ng/mL), the cytokines produced by cord blood CD4+ T cells in the presence of monocytes were measured by ELISA kits and the mRNA was detected by reverse transcription-polymerase chain reaction (RT-PCR) technique. Our results showed: CD4+ T cells in the presence of monocytes and isolated monocytes from the high-risk group produced a much greater amount of IL-6, either spontaneously or after stimulation, than did those of the low-risk group; CD4+ T cells of low-risk group produced a significantly greater amount of interferon gamma (IFN gamma) than did those from the high-risk group; IL-4 cannot be detected by ELISA kit, and only a trace amount of IL-4 mRNA was detected by RT-PCR technique; cord blood basophils stimulated with PHA and PMA could produce a significant amount of IL-4; there was an inverse correlation between the production of IFN gamma and cord blood IgE level (high-risk group, r = 0.647, n = 17) and the number of natural killer (NK) cells (CD3- CD16+ CD56+) was significantly lower in high-risk group than for low-risk group. Our data suggested increased production of IL-6 and decreased production of IFN gamma of cord blood mononuclear cells appear to be the hallmark of newborns from the high-risk population.

Soluble CD23 directly activates monocytes to contribute to the antigen-independent stimulation of resting T cells.

The majority of T cells at the site of an inflammatory lesion do not appear to be Ag-specific, but they still contribute to the inflammatory response. Herein, we report that sCD23 activates monocytes to participate in the stimulation of resting T cells in the absence of TCR engagement. First, sCD23 selectively triggers monokine release by purified monocytes in the absence of costimulus. It induces TNF-alpha, IL-1 beta, IL-8, granulocyte-macrophage-CSF, and prostaglandin E2 but no IL-10, IL-12, TGF-beta, or leukotriene B4. The sCD23-induced TNF-alpha production is significantly inhibited by IL-4 and IL-10 but not by TGF-beta. Also, monocytes activated by sCD23 express decreased levels of HLA-DR and increased levels of CD14, CD54, CD40, and B7 Ag. Next, we show that, in the presence of monocytes, sCD23 is a potent costimulator of IL-2 or IL-12-induced IFN-gamma production by resting T cells in the absence of exogenous Ag and that this effect is partially reduced by anti-TNF-alpha mAb. B cells cannot substitute for monocytes, and CD4+ and CD8+ T cells are equal responders. The data further indicate that monocyte-T cell contact, more particularly CD40-CD40L interactions, is required for IFN-gamma production in response to IL-2 plus sCD23, and the response to IL-12 plus sCD23 is CD40- and B7-independent but is still partially contact-dependent. It is proposed that sCD23, when produced locally at a site of immune response, may trigger an inflammatory process via monokine release and may further amplify it via the stimulation of bystander non-Ag-specific T cells.

Elimination of monocytes from cultures activated with recall antigens

Recent data provide evidence that antigen-specific CD4 + T-cell clones or antigen-activated T-cell lines can kill antigen-presenting cells (APC). We focused our studies on monocytes acting as APC in cultures of T cells freshly isolated from peripheral blood. The presence of monocytes in culture was monitored by their ability to emit light during phagocytosis of latex particles (latex-induced chemiluminescence). Using this approach as well as flow cytometry, evidence is presented that monocytes are eliminated from cultures with T cells activated with recall antigens (PPD or TT). The mechanism of monocyte elimination involved apoptosis as judged from in situ detection of DNA strand breaks by the terminal deoxynucleotidyl transferase assay. The antigen- but not lectin-dependent monocyte elimination was MHC-restricted and mediated by CD4 + T lymphocytes. This finding supports the hypothesis that elimination of APC is a general phenomenon during T-cell activation and may represent an important immunoregulatory mechanism.

The induction of bacillus-Calmette-Gu�rin-activated killer cells requires the presence of monocytes and T-helper type-1 cells

The induction of bacillus-Calmette-Gu�rin-activated killer cells requires the presence of monocytes and T-helper type-1 cells

Proliferative response and cytokine production of bovine peripheral blood mononuclear cells induced by the superantigens staphylococcal enterotoxins and toxic shock syndrome toxin-1.

The potential of staphylococcal enterotoxin A (SEA), B (SEB), C(SEC) and toxic shock syndrome toxin-1 (TSST-1) to act as superantigens by inducing polyclonal T-cell mitogenesis and cytokine production was tested on bovine peripheral blood mononuclear cells (PBMC). These four toxins were capable of inducing strong proliferative response of PBMC from calves over a broad dosage range (1 pg/ml to 1 microgram/ml) in vitro. The toxin-activated blast cells consisted of both CD4+ T-cells and CD8+ T-cells, but the T-cell proliferation depended upon the presence of monocytes. Treatment of monocytes with monoclonal antibody to major histocompatibility complex class II antigens substantially inhibited the toxin-induced T-cell proliferative response, but paraformaldehyde-fixation did not abrogate the accessory function. SEA, SEB, SEC and TSST-1, all induced the in vitro release of interleukin-2, interferon gamma and tumor necrosis factor alpha in a dose dependent manner. The results indicate that SEA, SEB, SEC and TSST-1 are capable of acting as superantigens by stimulating bovine T-cells as shown in the human and murine systems. The possible implications of these toxins in the immunopathogenesis of bovine mastitis caused by the infection with Staphylococcus aureus are discussed.

Immature CD45RA(low)RO(low) T cells in the human cord blood. I. Antecedents of CD45RA+ unprimed T cells.

A subset of resting T cells expressing low levels CD45RA and CD45RO molecules (< 1 x 10(3)/cell; CD45RA(low)CD45RO(low)) but high levels of CD45RB and CD38 (5 to 25 x 10(3)/cell) were identified in human cord blood. When these CD45RA(low)RO(low) cells were isolated, they failed to survive in culture (< 10% viability at day 3) unless they were co-cultured on fibroblast monolayers. During the co-culture with fibroblasts, these lymphocytes acquired high levels of cytoplasmic and then membrane CD45RA by day 3 without signs of activation. When stimulated with PHA in the absence of fibroblasts the CD45RA(low)RO(low) cells required monocytes or IL-1 to respond; they rapidly perished if neither were present. On optimal mitogenic stimulation for 48 h in the presence of monocytes, > 90% of CD45RA(low)RO(low) T cells showed only transient CD45RA expression and rapidly acquired CD45RO reactivity. After activation for 48 h the stimulated CD45RA(low)RO(low) subset synthesized high levels of IL-2, comparable to mature peripheral T cells. No IL-4 was detected in these stimulated cultures of cord blood T cells. These data taken together suggest that CD45RA(low)RO(low) T cells in the cord blood are the relatively immature antecedents of CD45RA+RO T cells that require stromal factors for survival in a resting state. The same cells need monocytes or IL-1 for their activation to develop after a short CD45RA+ stage into activated CD45RO+RA(low) T cells with potent IL-2 biosynthetic capacity. An additional study of these cells is warranted to confirm that they are in fact the recent emigrants from the thymus, as suggested by similar observations in animal models.

Vascular contractile potency of endothelin-1 is increased in the presence of monocytes or macrophages

Accumulation of inflammatory cells and altered responsiveness to vasoactive mediators are commonly observed events in atherosclerotic vessels. We studied the effect of monocytic cells on endothelin-1 (ET-1)-induced contraction of strips of guinea pig carotid artery. The vascular contractile potency of ET-1 was increased markedly in the presence of human peripheral blood monocytes, guinea pig alveolar macrophages (M phi), and the human monocytic cell line, THP-1. Specific binding of 125I-labeled ET-1 to these cells was detected, and Scatchard analysis indicated a dissociation constant value of approximately 1 nM. In contrast, the human monocytic cell line, U-937, failed to bind 125I-ET-1 and did not alter ET-1 potency, suggesting that the ability of monocytic cells to increase ET-1 potency requires expression of ET receptors. Selective inhibition of ET-1 binding to vascular smooth muscle with BQ-123, an ETA receptor antagonist that does not inhibit ET-1 binding to monocytes, resulted in complete inhibition of vascular contraction. These data indicate that ET-1-induced vasoconstriction may be increased by monocytic cells via stimulation of monocyte endothelin receptors.

Histaminergic regulation of antibody-dependent cellular cytotoxicity of granulocytes, monocytes, and natural killer cells

We investigated effects of the biogenic diamine histamine on antibody-dependent cellular cytotoxicity (ADCC) against autologous anti-D-coated red blood cells mediated by human granulocytes, monocytes, and natural killer (NK) cells. Effector cells were separated from peripheral blood by countercurrent centrifugal elutriation. ADCC of monocytes and neutrophilic granulocytes was suppressed by histamine. ADCC of enriched CD3-/56+ NK cells was unchanged by histamine. ADCC of NK cells was effectively inhibited by elutriated monocytes or neutrophils. Histamine completely reversed the inhibition of NK cell-mediated ADCC induced by monocytes and partly reversed the inhibition induced by neutrophils; thereby, histamine augmented ADCC of NK cells in the presence of monocytes or neutrophils. The indirect effect of histamine on ADCC of NK cells and the effect of histamine on ADCC of monocytes/neutrophils were completely antagonized by the specific H2 receptor (H2R) blocker ranitidine. We conclude that activation of H2R suppresses ADCC reactivity of monocytes/neutrophils and, concomitantly, promotes ADCC reactivity of NK cells by abrogating a phagocyte-derived, suppressive signal.

Human IL-10 reduces the number of IL-4-induced IgE B cells in cultures of atopic mononuclear cells.

We investigated the effect of recombinant human IL-10 on IL-4- and antigen-driven human peripheral blood mononuclear cell cultures derived from atopic donors. These cultures were phenotyped for the percentage of B cell (CD20 HLA-DR) population by flow cytometry and for intracellular IgE using epifluorescence microscopy. The addition of IL-4 (100 U/ml) to these cultures resulted in an increase in the percentage of IgE B cells. However, the percentage of IgE B cells in cultures coincubated with IL-10 (2 or 20 ng/ml) and IL-4 was reduced to the level of medium control. Peripheral-blood mononuclear (PBMN) cultures driven with dust mite allergen demonstrated a significant increase in cellular proliferation, as measured by 3[H] thymidine uptake, and in the percentage of IgE B cells. The coaddition of IL-10 (2 or 20 ng/ml) to these cultures significantly inhibited both proliferation and the mean percentage of IgE B cells. The inhibitory effect of IL-10 on IgE B cell percentages in both the IL-4- and the allergen-driven cultures, and on allergen-driven proliferation, was dependent upon the presence of monocytes. Interestingly, the inhibitory effect of IL-10 on allergen-driven proliferation in the atopic PBMN cultures was reversible by the coaddition of exogenous IFN gamma (1 ng/ml) and IL-2 (2 U/ml). The addition of IL-2 (2 U/ml) partially reversed IL-10-inhibited allergen-driven proliferation while alone IFN gamma had no effect (1 ng/ml). In fact, the addition of IFN gamma (1 ng/ml) in the absence of either IL-10 or IL-2 (2 U/ml) partially inhibited allergen-driven proliferation.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-CD3-Activated T Cells from Chronic Nonviremic HBV Carriers Are Hyperreactive to Monocytic Accessory Signals

We analyzed T cell responses through the CD3 activation pathway in a group of chronic HBV carriers. PBMC stimulated with the mAb OKT3 showed higher proliferative response in HBV-DNA(-) carriers compared to HBV-DNA(+) carriers and to controls. In contrast, no differences in proliferative responses were observed between HBV-DNA(-) carriers and controls in cell cultures stimulated with immobilized 64.1 mAb (SPB-64.1) which induces proliferation in the absence of monocytes. We further examined T cell responses in the presence of monocytes and their soluble factors to immobilized OKT3 mAb (SPB-OKT3). Purified T cells did not proliferate to SPB-OKT3. When autologous monocytes were added, higher proliferative response, IL-2 production, and IL-2 receptor expression were observed in HBV-DNA(-) carriers than in controls. An enhanced cell proliferation was also obtained when monocyte supernatants were added to T cells cultured with SPB-OKT3. Moreover, when IL-6 alone or combined with IL-1 way added to SPB-OKT3-stimulated T cell cultures, a significantly higher increase in T cell proliferation was detected in HBV-DNA(-) carriers. Our results thus show a T cell hyperreactivity to accessory signals from monocytes (mainly IL-6) in HBV-DNA(-) carriers, that is probably related to an ongoing viral clearance.

Modulation of T Cell Production of Interferon-γ by Human Monocytes: Effect of Engagement of CD14 on Monocytes

It has been suggested that CD14 might have influences on a variety of immunoregulatory functions of monocytes. The current studies therefore examined in detail the immunoregulatory roles of CD14 by studying the effects of anti-CD14 mAb. Anti-CD14 mAb suppressed the monocyte-dependent interferon-γ (IFN-γ) production by CD4 + T cells induced by soluble anti-CD3. Although anti-CD14 mAb also suppressed the IL-6 production by monocytes, the inhibition of the IFN-γ production induced by soluble anti-CD3 was not restored by addition of exogenous IL-6 or factors generated from cultured monocytes. Of note, anti-CD14 mAb decreased the expression of CD54, but not that of CD11a or CD18, on monocytes, suggesting that inhibition of the soluble anti-CD3-induced IFN-γ production by anti-CD14 mAb might be a result from decrease in CD11a/CD18-CD54-mediated interactions between CD4 + T cells and monocytes. By contrast, anti-CD14 mAb enhanced the IFN-γ production by immobilized anti-CD3-activated CD4 + T cells in the presence of monocytes. This enhancement of the IFN-γ production required physical contact between monocytes and T cells, which does not involve MHC class II antigen-CD4 interactions. These results indicate that CD14 on monocytes plays a variety of immunomodulatory functions depending upon the nature of stimulation. The data thus demonstrated the presence of several different interactions between monocytes and T cells that regulate the T cell cytokine production.