Spontaneous production of gamma-interferon in cultures of T lymphocytes obtained from patients with Beh?et's disease

The spontaneous production of interferon (IFN) in the cultures of peripheral blood mononuclear leukocytes (PBML) obtained from 30 patients with Beh?et's disease was investigated. PBML obtained from each of 26 patients in the convalescent stage and four patients in the exacerbation stage were cultured at least twice without stimulation, and IFN activity in the culture fluid 2 to 7 days after the cultivation was assayed. Twenty PBML of normal healthy donors were also cultured simultaneously. PBML of all patients in the convalescent stage spontaneously produced high-titered IFN (60.0 +/- 9.5 IU/ml), but IFN activity produced in PBML cultures of four patients in the exacerbation stage was very low or was undetectable. Similarly, IFN was always detectable in the circulation of the patients whose PBML spontaneously produced IFN. All IFN activity detected both in the circulation and in the fluid of PBML culture from these patients was gamma-IFN, defined by virtue of its acid lability and antigenicity neutralized with antiserum for gamma-IFN and not with antisera for alpha- and beta-IFN. The cellular source of this gamma-IFN in the patients' PMBL was T lymphocytes and not non-T cells or macrophages. T lymphocytes did not require the help of macrophages. It is suggested that T lymphocytes of these patients may be stimulated by unknown causative agents in vivo and may produce gamma-IFN in vivo as well as in in vitro culture of T lymphocytes.     

gamma Interferon production appears to predict time of recurrence of herpes labialis

Peripheral blood mononuclear cells separated from the blood of 29 volunteers within 3 wk of the onset of recurrent oral herpes labialis spontaneously secreted IFN-gamma (and small amounts of IFN-beta) into the culture medium in varying amounts (mean = 77 U/ml, SE = 17). However, interferon could not be detected in the serum of 10 of these patients tested. In the group as a whole, peak levels of interferon were secreted in vitro at 6 to 20 days after the onset of herpes labialis. Serial studies in eight patients showed peak production in the second or third week, with subsequent decrease to undetectable levels at 6 wk. A strong correlation between peak supernatant interferon level and the time to the next recurrence of herpes labialis in each patient was noted (r = 0.82, p less than 0.0001). Herpes simplex antigen-stimulated mononuclear cell cultures from each patient produced a mixture of IFN-alpha and IFN-gamma. A less marked but still significant correlation was noted between the peak mixed interferon level and the inter-recurrence interval (r = 0.52, p less than 0.005). These results suggest that a recurrent herpes labialis acts as an in vivo stimulus to the induction of IFN-gamma-producing cells that circulate in peripheral blood. The IFN-gamma produced is either a direct determinant of frequency of recurrence of herpes or a quantitative marker for other cellular immune events determining frequency.     

The regulation of gamma-interferon production by interleukins 1 and 2

Purified interleukins 1 and 2 (IL-1 and IL-2) were used to investigate their role in the production of gamma-interferon (gamma-IFN). Macrophage depletion from human peripheral blood mononuclear leukocytes (PBML) inhibited gamma-IFN production. Addition of purified IL-1 partially restored IFN production of macrophage-depleted PBML induced by three T cell mitogens (phytohemagglutinin, PHA; concanavalin A, con A; and staphylococcal enterotoxin A, SEA), but had no effect on induction of IFN production by undepleted PBML. Therefore endogenous IL-1 production by macrophages is probably one of the mechanisms by which they act as accessory cells for IFN production by lymphocytes. A monoclonal antibody 9.6 which binds to the sheep erythrocyte (E) receptor found on human T cells inhibited IFN production. Addition of IL-2, but not IL-1, was found to reverse this inhibition. Prostaglandin E2, a macrophage product, inhibited gamma-IFN production induced by PHA, Con A, and OKT3 but usually not SEA. This inhibitory effect was reversible by the addition of IL-2 but not IL-1. In the absence of mitogen IL-1 alone rarely induced any IFN production, although some IFN was produced by PBML from a small minority of donors. Without mitogen IL-2 induced IFN production only at very high concentrations and the added presence of IL-1 did not enhance this induction.     

Leu-3+ T cells produce gamma-interferon in patients with recurrent herpes labialis

Interferon-gamma (IFN-gamma) was spontaneously secreted by peripheral blood mononuclear cells cultured from patients soon after recurrent herpes labialis (RHL) or was induced from macrophage-T lymphocyte cultures in vitro with HSV antigen. Circulating Leu-3+/Leu-2- cells produced the spontaneous IFN almost exclusively. In the HSV antigen-stimulated culture system the same subset was the predominant producer of IFN-gamma. The IFN-gamma producing leu-3+ lymphocytes were plastic nonaderent but nylon wool adherent, and may be analagous to the murine Th 2 helper cell. In contrast to one lymphocyte subset being the major IFN-gamma producer in this viral disease, mitogen stimulation induced IFN-gamma from all (Leu-2+/2- and Leu-3+/3-) subsets, with panning as the separation technique. As mitogens circumvent the normal processing and presentation of antigen, the RHL system described above may provide a more accurate picture of the relative contributions of helper (Leu-3+) and cytotoxic/suppressor (Leu-2+) T cells to IFN-gamma production in herpes viral disease.     

Role of interferon-gamma in inducing cytotoxicity of peripheral blood mononuclear leukocytes to bovine herpesvirus type 1 (BHV-1)-infected cells

In the present study, the possible role of interferon (IFN)-gamma on the induction of cytotoxic activity of peripheral blood mononuclear leukocytes (PBML) from BHV-1-immune cattle was investigated. Supernatants obtained from BHV-1-immune PBML, stimulated under conditions similar to those required to demonstrate cytotoxicity, contained an antiviral substance capable of inducing 2'-5'-oligoadenylate synthetase activity in MDBK cells and MHC class II antigen expression on epithelial cells. These supernatants also contained IFN-alpha, but were devoid of tumor necrosis factor and interleukin-2 biological activities. Further studies during primary infection and hyperimmunization with BHV-1 showed that IFN-gamma production and non-MHC-restricted cytotoxicity against BHV-1-infected targets always occurred concomitantly, suggesting that they represent an important part of the detectable CMI responses mounted against this virus. Furthermore, it was also demonstrated that cytotoxicity of PBML against BHV-1-infected cells was reduced with the addition of antibodies to bovine IFN-gamma to the cytotoxic assay. Bovine recombinant IFN-gamma was able to enhance the in vitro cytotoxic activity of PBML from immune cattle, but not from their nonimmune counterparts. This suggests that other factors, in addition to IFN-gamma, may be essential in the development of non-MHC-restricted cytotoxic responses during BHV-1 infection.     

Role of specific innate immune responses in herpes simplex virus infection of the central nervous system

Herpes simplex virus 1 (HSV-1) causes a spectrum of disease, including herpes labialis, herpes keratitis, and herpes encephalitis, which can be lethal. Viral recognition by pattern recognition receptors plays a central role in cytokine production and in the generation of antiviral immunity. The relative contributions of different Toll-like receptors (TLRs) in the innate immune response during central nervous system infection with HSV-1 have not been fully characterized. In this study, we investigate the roles of TLR2, TLR9, UNC93B1, and the type I interferon (IFN) receptor in a murine model of HSV-1 encephalitis. TLR2 is responsible for detrimental inflammatory cytokine production following intracranial infection with HSV-1, and the absence of TLR2 expression leads to increased survival in mice. We prove that inflammatory cytokine production by microglial cells, astrocytes, neutrophils, and monocytes is mediated predominantly by TLR2. We also demonstrate that type I IFNs are absolutely required for survival following intracranial HSV-1 infection, as mice lacking the type I IFN receptor succumb rapidly following infection and have high levels of HSV in the brain. However, the absence of TLR9 does not impact survival, type I IFN levels, or viral replication in the brain following infection. The absence of UNC93B1 leads to a survival disadvantage but does not impact viral replication or type I IFN levels in the brain in HSV-1-infected mice. These results illustrate the complex but important roles that innate immune receptors play in host responses to HSV-1 during infection of the central nervous system.     

Variation in the WBC differential count and other factors associated with reporting of herpes labialis: a population-based study of adults

Reactivation of latent herpes virus has been linked to triggers of mild immunosupression, such as stress or UV-exposure. Despite having predictive value in severe immunodeficiency, the white blood cell (WBC) differential count has not been examined in relation to risk of herpes reactivation in population studies. The WBC differential count and other risk factors for herpes labialis were examined in 5687 adults (ages 18-64) from the Third National Health and Nutrition Examination Survey, who had WBC 3.5-11 x 10(6) cells mL(-1) and reported no acute infections in the past month. The association between self-reported herpes labialis in the past year and the WBC differential count was modeled, adjusting for age, sex, race/ethnicity, education, smoking, upper respiratory infections (URI), and HSV-1 antibodies. Herpes labialis was significantly associated with white race/ethnicity, being a nonsmoker, and frequent URI. Compared with the highest quartile, being in the lowest quartile of granulocytes was associated with herpes labialis, adjusted odds ratio=1.82 (95% confidence interval 1.20, 2.28). At the same time, there was a trend towards an inverse association of lower lymphocyte count and herpes labialis. These findings suggest that moderate differences in the WBC differential count are related to reactivation of HSV-1. Prospective studies may help to show whether such differences indicate susceptibility to loss of latency or represent a consequence of reactivated infection.     

Native and recombinant herpes simplex virus type 1 envelope proteins induce human immune T-lymphocyte responses.

The abilities of whole herpes simplex virus type 1 (HSV-1) antigen (HSV-ag) and purified HSV-1 native and recombinant envelope proteins to stimulate in vitro T-lymphocyte responses were compared in patients with recurrent herpes labialis. Immunochemically purified preparations of native glycoproteins B, C, and D (ngB, ngC, ngD) from cultured HSV-1 as well as expressed recombinant plasmid preparations of gD (rgD-1t, rgD-45K) elicited lymphocyte proliferation (LT) and production of gamma interferon (IFN-gamma) and interleukin-2 (IL-2) only in seropositive individuals. The IFN-gamma induced by rgD-1t correlated with the time to the next herpetic lesion in 19 volunteers followed to recurrence (r = 0.69, P less than 0.008), although the magnitude and frequency of LT and IFN-gamma responses were lower with either recombinant or native purified antigens than with the whole-virus antigen. Combinations of ngB plus ngD or ngB plus ngC plus ngD stimulated more IFN-gamma, equivalent to whole-virus-antigen responses. Recombinant-derived human IL-2 also specifically increased LT and IFN-gamma responses in antigen-driven cultures. ngD stimulated IL-2 and LT responses similar to those of whole-virus antigen and higher than those of ngC. HSV-ag and ngB induced significantly higher titers of total IFN than could be accounted for by IFN-gamma; this was not seen for the other antigens, which induced only IFN-gamma. HSV-ag-driven Leu 2a-, plastic-nonadherent blood cells, unlike whole peripheral blood mononuclear cells, showed evidence of an increase and then a decline in the frequency of HSV-responsive cells after a lesion recurrence. These studies suggest that HSV-1 envelope proteins are capable of stimulating an immune T-helper-cell response which is associated with the prevention of human herpes simplex lesion recurrence. Although the whole virus probably contains additional important antigens, increasing concentrations or combinations of certain purified glycoproteins or the addition of nonspecific enhancers of T-lymphocyte function can drive in vitro immune responses to the same level as the complete set of viral antigens.     

Successful treatment of herpes labialis with topical acyclovir.

A double blind, placebo controlled trial of 5% acyclovir cream, applied topically five times a day for five days, was carried out in 49 patients with recurrent herpes labialis. These patients had a total of 74 episodes, 34 of which were treated with the 5% acyclovir cream and 40 with matching placebo. First episodes and all episodes treated with acyclovir cream had significantly shorter times to formation of ulcer or crust and to complete healing (p less than 0.05 for all variables). The duration of all symptoms and proportion of patients developing itching was also reduced by acyclovir cream in first episodes, though the difference was not significant. When the patient started treatment early in the course of a first episode acyclovir cream significantly reduced the percentage of lesions progressing beyond the papular stage (p less than 0.05). Acyclovir cream is well tolerated and effective for the treatment of recurrent herpes labialis.     

Nitric oxide production in murine spleen cells: role of interferons and prostaglandin E(2) in the generation of cytotoxic activity

The production of nitric oxide (NO) was measured in cultures of spleen cells stimulated by lipopolysaccharide (LPS), IL-2 or LPS + IL-2. We observed that NO synthesis is increased by IFN-gamma but inhibited by IFN-alpha/beta. This is not the case when IL-2 is present in the cultures, since interferons play a minor role in the regulation of the NO production. When IL-2 and LPS were associated in the cultures, the IFN-alpha/beta role seems more important than that of IFN-gamma. PGE(2) inhibits NO production in LPS supplemented cultures but has a slight effect in the presence of IL-2 and no effect with IL-2 + LPS. 3-isoButyl-1-methylxanthine (IBMX), an inhibitor of phosphodiesterases, induces a decrease of IFN production. In the presence of H-7, an inhibitor of protein kinase C (PKC), NO production is reduced when the cultures are supplemented by LPS or IL-2 but not when IL-2 and LPS are both added. H-7 also reduced IFN production. In the presence of N(G)-monomethyl-L-arginine (N-MMA), an inhibitor of NO synthesis, IFN production was increased, with no change in the cytotoxic activity. Hence, interferons regulate NO production by mouse spleen cells and, in return, NO modulates the generation of IFN.     

Cyclosporin A inhibits the production of gamma interferon (IFN gamma), but does not inhibit production of virus-induced IFN alpha/beta

The effect of cyclosporin A (CsA) on the production of gamma interferon (IFN gamma) versus IFN alpha/beta was studied using mouse and human lymphocytes and fibroblasts. Spleen cells from C57Bl/6 mice produced low but significant levels (40-60 U/ml) of IFN gamma after 2 to 3 days of culture with irradiated DBA spleen cells. The addition of CsA at concentrations as low as 0.1 microgram/ml completely inhibited (less than 10 U/ml) IFN gamma production in these cultures. High levels of IFN gamma (170-1200 U/ml) were produced when either C57Bl/6 spleen cells or Ficoll-Hypaque-purified human peripheral blood lymphocytes (PBL) were cultured with the T-cell mitogen staphylococcal enterotoxin A (SEA). The addition of CsA (0.1 microgram/ml) to these cultures also completely inhibited (less than 10 U/ml) IFN gamma production. This inhibition was shown not to be due to a change in the kinetics of IFN gamma production or to a change in the amount of SEA required for stimulation. IFN gamma production in SEA-stimulated mouse spleen cells was inhibited at 3 days of culture even when CsA was added at 24 or 48 hr postculture initiation. Thus, CsA inhibits IFN gamma production even when early events associated with lymphocyte activation have been allowed to take place. In contrast to IFN gamma production, IFN alpha/beta production by Newcastle disease virus (NDV)-infected mouse and human lymphocytes or fibroblasts was not inhibited by the addition of CsA (1 microgram/ml). CsA also did not block the action of IFN gamma or IFN alpha/beta since addition of CsA (1 microgram/ml) to reference IFN standards had no effect on their antiviral activity. Thus, CsA inhibits the production of IFN gamma by T cells but appears to have no effect on the production of IFN alpha/beta by virus-infected cells or on the antiviral action of already produced IFN gamma and IFN alpha/beta.     

Participation of macrophages in enhanced in vitro immune interferon (IFN gamma) production with mouse spleen cells

IFN gamma production in cultures of spleen cells obtained from mice sensitized with TH69, a live Streptococcus faecalis preparation, was examined to determine how macrophages participate. It was demonstrated that sensitized spleen macrophages participated in enhanced IFN gamma production by T cells at an early stage (0-6 hr) of incubation, and that this production is mainly dependent on Ia-bearing macrophages In the reconstitution experiments where different combinations of spleen macrophages and T cells obtained from mice sensitized with TH69, OK-432, and BCG were used, T cells required that the identity between the sensitizing organisms in vivo and the stimulating organisms in vitro be the same for enhanced IFN gamma production while macrophages did not. Macrophage-mediated production of IFN gamma appears to be genetically restricted because IFN gamma was only produced in cultures where the H-2 region of macrophages and T cells matched. Further examination revealed that for macrophages to participate in enhanced IFN gamma production, first contact between cycloheximide-treated macrophages and T cells was required. Second, enhanced IFN gamma production occurred when culture supernatants of macrophages obtained from sensitized spleen cells were added to T cells. However, the addition of culture supernatant obtained from sensitized peritoneal macrophages resulted in inhibition of IFN gamma production. These results clearly showed the crucial role of macrophages in enhanced IFN gamma production by spleen T cells in vitro.     

Interferon induction in marrow-derived macrophages: regulation by L cell conditioned medium

Mouse bone marrow cells grown in medium enriched with L cell conditioned medium (LCM) as a source of colony stimulating factor (CSF) yield populations of adherent macrophages which are quite sensitive to induction of interferon (IFN) by viral and nonviral inducers. We examined the role of LCM in the sensitivity of marrow macrophage cultures to IFN induction. Removal of LCM from the cultures for as little as 3 hours markedly reduced the IFN titers induced by a double stranded ribopolynucleotide (poly I:C) or a lipopolysaccharide (LPS), while induction by Newcastle disease virus (NDV) was unaffected. Addition of anti-CSF serum to LCM medium also reduced IFN titers in response to polyI:C but had no effect on NDV induction. The inhibitory effect of anit-CSF indicates that the LCM requirement is at least partially related to the colony stimulating activity of the medium. We postulate that CSF regulates the initial interaction of macrophages with polyI:C or LPS rather than the synthesis and secretion of interferon by the phagocytes. Nearly complete restoration of IFN induction with polyI:C was obtained when LCM deprived cultures were reincubated with LCM medium previously conditioned by marrow cultures.     

Balm mint extract (Lo-701) for topical treatment of recurring herpes labialis.

A double-blind, placebo-controlled, randomized trial was carried out with the aim of proving efficacy of standardized balm mint cream [active ingredient: 1% Lo-701--dried extract from Melissa officinalis L. leaves (70:1)] for the therapy of herpes simplex labialis. Sixty six patients with a history of recurrent herpes labialis (at least four episodes per year) in one center were treated topically; 34 of them with verum and 32 with placebo. The cream had to be smeared on the affected area four times daily over five days. A combined symptom score of the values for complaints, size of affected area and blisters at day 2 of therapy was formed as the primary target parameter. There was a significant difference in the values of the primary target parameter between both treatment groups: verum 4.03 +/- 0.33 (3.0); placebo 4.94 +/- 0.40 (5.0); values given are mean +/- SEM (median) of the symptoms score on day 2 of therapy. The tested formulation is effective for the treatment of herpes simplex labialis. The significant difference in the combined symptom score on the second day of treatment is of particular importance having in mind that the complaints in patients suffering from herpes labialis are usually most intensive at that time. In addition to the shortening of the healing period, the prevention of a spreading of the infection and the rapid effect on typical symptoms of herpes like itching, tingling, burning, stabbing, swelling, tautness and erythema, the balm mint cream has a further advantage. The different mechanism of action of the balm mint extract rules out the development of resistance of the herpes virus. Some indication exists that the intervals between the periods with herpes might be prolonged with balm mint cream treatment.     

Effect of herbal therapy on herpes labialis and herpes genitalis

Administration of hot water extracts of six herbs to four patients with recurrent herpes labialis led to prompt crusting over and complete recovery within a few days. Similar treatment for one female patient who had been suffering from recurrent genital herpes resolved the associated pain dramatically. In all cases mentioned, symptoms disappeared much more quickly than with previous outbreaks when herb extracts were not administered.     

缺失ORF73或ORF214基因对重组鸡痘病毒免疫应答的影响

【目的】旨在研究鸡痘病毒ORF73和ORF214编码蛋白是否具有IL-18结合蛋白的功能,以及ORF73或ORF214基因缺失后对重组病毒诱导免疫应答的影响。【方法】以缺失ORF73或ORF214基因并表达H5亚型AIVHA基因的重组鸡痘病毒(rFPVLP-△73LRH5A、rFPVLP-△214LRH5A)作为研究对象,以未缺失ORF73或ORF214基因而表达H5亚型AIVHA基因的重组鸡痘病毒(rFPVLP-12LSH5A)作为对照,检测重组病毒体外诱导SPF鸡脾细胞和外周血淋巴细胞产生IFN情况,同时检测重组病毒免疫SPF鸡后诱导的体液免疫、CD4+/CD8+比值、外周血淋巴细胞的增殖能力和H5亚型AIV强毒攻击后的免疫保护效力。【结果】rFPVLP-△73LRH5A和rFPVLP-△214LRH5A体外诱导脾细胞产生的IFN量显著高于rFPVLP-12LSH5A,而免疫10d后的CD4+/CD8+比值显著低于rFPVLP-12LSH5A;3种重组鸡痘病毒诱导外周血淋巴细胞增殖的能力没有明显差异;3种重组病毒在SPF鸡均产生针对H5亚型AIV的HI抗体,免疫14d后rFPVLP-△214LRH5A组诱生的HI抗体水平显著低于rFPVLP-12LSH5A组的抗体,但3组在免疫21d后HPAIV的致死性攻击时,均100%被保护。【结论】鸡痘病毒ORF73和ORF214编码蛋白具有IL-18结合蛋白抑制IFN产生的功能,虽然缺失株和亲本株重组鸡痘病毒在细胞和体液免疫应答存在一定差异,但在SPF鸡均能诱导产生良好的免疫保护。     

Serum-Dependent Enhancement of Coxsackievirus B4-Induced Production of IFNα, IL-6 and TNFα by Peripheral Blood Mononuclear Cells

Only a few reports have been published on the interactions between Coxsackievirus B4 (CVB4) and human peripheral blood mononuclear cells (PBMC) but have not been extensively documented. Human serum containing non-neutralizing anti-CVB4 antibodies increased CVB4-induced synthesis of IFNα by PBMC. In this study, we determined if CVB4 and human serum have the ability to activate inflammatory cytokines in addition to IFNα in PBMC cultures. PBMC from healthy donors were inoculated with infectious, inactivated CVB4 or with CVB4 incubated with dilutions of human serum or polyvalent IgG with anti-CVB4 activity. Levels of IFNα, TNFα, IL-6, IL-12, IFNγ and IL-10 in the cell-free supernatants of PBMC cultures were measured using ELISA. Infection was assessed by real-time PCR. PBMC inoculated with CVB4 produced inflammatory cytokines but not IFNα. When CVB4 was incubated with serum or IgG, IFNα was detected in the culture supernatants, and high concentrations of TNFα and IL-6 were measured. The concentrations of TNFα and IL-6 were not reduced in cultures inoculated with inactivated CVB4, whereas the IgG-dependent enhancement of IFNα, IL-6 and TNFα production with inactivated virus was suppressed. The potentiation of IFNα production was associated with a high intracellular viral load. Infectious and non-infectious CVB4 can induce the production of inflammatory cytokines but not IFNα by PBMC. High levels of IFNα, in addition to TNFα and IL-6, in culture supernatants were obtained when infectious CVB4 was combined with immune serum or IgG, and they were associated with high amounts of intracellular viral RNA.     

Analysis of the time course of IFN-gamma mRNA and protein production during primary murine listeriosis. The immune phase of bacterial elimination is not temporally linked to IFN production in vivo

IFN-gamma clearly plays an important role in the murine host response against Listeria monocytogenes, but the time course of its production and its precise role in immunity remain controversial. To address these issues, we sequentially monitored IFN production and bacterial accumulation in vivo in C57B1/6 mice during primary listeriosis. IFN-gamma mRNA levels (measured by Northern blot analysis of freshly isolated splenic RNA) and serum IFN (measured by ELISA) were both maximal on day 1 of infection, decreasing steadily after day 2 to barely detectable levels by days 4 to 6. Significantly, there was no direct relationship between IFN levels and listericidal activity in vivo. Between days 1 and 3, the period of maximal IFN production, host bacterial load (assessed by quantitating live L. monocytogenes/spleen) increased approximately 10- to 50-fold. On the other hand, during the immune phase of infection (between days 5 and 7), a period when both IFN mRNA and protein were barely detectable, the host bacterial load decreased 1,000- to 10,000-fold. The paucity of IFN production in vivo during the immune phase was unexpected in light of previous reports demonstrating abundant in vitro lymphokine release by splenocytes isolated during the same time period. By direct comparisons of IFN production in vivo and in vitro, however, we could show that the late (days 6-7) peak of IFN release observed in Ag-stimulated cultures was an in vitro artifact. By contrast the pattern of spontaneous IFN release (obtained when freshly isolated cells were incubated in the absence of Ag) conformed more closely to that observed in vivo. Because listerial Ag stimulated vigorous lymphokine release in vitro, we sought to determine whether an analogous effect could be observed in vivo. In fact, even the infusion of very large doses of live bacteria (5-20,000,000/mouse) did not stimulate endogenous IFN-gamma production in mice infected for 6 to 7 days. These studies suggest three major conclusions: 1) IFN production in vivo occurs primarily during the early phase of listeriosis; 2) the dramatic decrease in bacterial numbers observed late in infection cannot be directly attributed to increased IFN production by LM-immune T cells; 3) although Ag-driven cultures of freshly isolated cells can provide useful information about the potential lymphokine-producing capabilities of Ag-specific T cells, these results have limited relevance in understanding patterns of T cell lymphokine production in vivo.     

Interferon-mediated inhibition of human polyclonal immunoglobulin synthesis

Human lymphoblastoid IFN suppressed human polyclonal Ig synthesis in a dose-related manner, with 71% mean inhibition of antibody production found when 1000 units of IFN were added to the cultures. This suppression was demonstrated to be mediated by an electrophoretically pure preparation of IFN. Furthermore, IFN inhibition of both the T-dependent and the T-independent polyclonal activators was not the result of direct cellular cytotoxicity. IFN-mediated suppression of human polyclonal Ig production does not result from induction of T suppressor cells, and in a T helper cell-independent system this inhibition appears to result from either a direct action on the B cells or an indirect effect via monocytes.