Immunoglobulin G Fc Receptors Research Articles

The solution structure of the unbound IgG Fc receptor CD64 resembles its crystal structure: Implications for function.

FcγRI (CD64) is the only high-affinity Fcγ receptor found on monocytes, macrophages, eosinophils, neutrophils and dendritic cells. It binds immunoglobulin G (IgG) antibody-antigen complexes at its Fc region to trigger key immune responses. CD64 contains three immunoglobulin-fold extracellular domains (D1, D2 and D3) and a membrane-spanning region. Despite the importance of CD64, no solution structure for this is known to date. To investigate this, we used analytical ultracentrifugation, small-angle X-ray scattering, and atomistic modelling. Analytical ultracentrifugation revealed that CD64 was monomeric with a sedimentation coefficient s020,w of 2.53 S, together with some dimer. Small-angle X-ray scattering showed that its radius of gyration RG was 3.3-3.4 nm and increased at higher concentrations to indicate low dimerization. Monte Carlo modelling implemented in the SASSIE-web package generated 279,162 physically-realistic trial CD64 structures. From these, the scattering best-fit models at the lowest measured concentrations that minimised dimers revealed that the D1, D2 and D3 domains were structurally similar to those seen in three CD64 crystal structures, but showed previously unreported flexibility between D1, D2 and D3. Despite the limitations of the scattering data, the superimposition of the CD64 solution structures onto crystal structures of the IgG Fc-CD64 complex showed that the CD64 domains do not sterically clash with the IgG Fc region, i.e. the solution structure of CD64 was sufficiently compact to allow IgG to bind to its high-affinity Fcγ receptor. This improved understanding may result in novel approaches to inhibit CD64 function, and opens the way for the solution study of the full-length CD64-IgG complex.

IgG targeting distinct seasonal coronavirus- conserved SARS-CoV-2 spike subdomains correlates with differential COVID-19 disease outcomes.

Despite SARS-CoV-2 being a “novel” virus, early detection of anti-spike IgG in severe COVID-19 patients may be caused by the amplification of humoral memory responses against seasonal coronaviruses. Here, we examine this phenomenon by characterizing anti-spike IgG responses in non-hospitalized convalescent individuals across a spectrum of COVID-19 severity. We observe that disease severity positively correlates with anti-spike IgG levels, IgG cross-reactivity against other betacoronaviruses (β-CoVs), and FcγR activation. Analysis of IgG targeting β-CoV-conserved and non-conserved immunodominant epitopes within the SARS-CoV-2 spike protein revealed epitope-specific relationships: IgG targeting the conserved heptad repeat (HR) 2 region significantly correlates with milder disease, while targeting the conserved S2′FP region correlates with more severe disease. Furthermore, a lower HR2-to-S2′FP IgG-binding ratio correlates with greater disease severity, with ICU-hospitalized COVID-19 patients showing the lowest HR2/S2′FP ratios. These findings suggest that HR2/S2′FP IgG profiles may predict disease severity and offer insight into protective versus deleterious humoral recall responses.

The therapeutical approaches for rare diseases through the immune processes of IgG Fc Receptors

Fc Receptor for Immunoglobulin G (IgG) is the major class among the five classes of Fc receptors including Fc Receptor for IgA, IgE, IgM and IgD.

Analysis of the linear epitope for Fc-binding on the mouse IgG Fc receptor (moFcγRI) by synthetic peptide.

To identify the linear epitope for Fc-binding to the mouse immunoglobulin G (IgG) Fc receptor (moFcγRI), peptides derived from the membrane-distal extracellular domain (EC2) of moFcγRI, corresponding to the homologous region of human FcγRI (huFcγRI) and huFcγRII, were synthesized. Using a dot-blot assay, six peptides were tested. The results showed that the moRI3 peptide (CVFYRNGKSFQFS) could combine with mouse IgG efficiently. A competitive enzyme-linked immunosorbent assay (ELISA) showed that the IC50 value of the moRI3 peptide was 38.03 mM. The moRI3 peptide could inhibit the combination of mouse IgG to the transfected COS 7 cells significantly with an IC50 value of 72.68 mM. The IgG-binding region of moFcγRI was also localized in the C'-E loop of the EC2 domain as predicted according to huFcγRI and huFcγRII. We predicted that the minimum effective IgG-binding region of moFcγRI may be the peptide 153SFQFSS158. The linear epitope for immunoglobulin-binding to mouse FcγR is also described. Thus, we generated a peptide that targets a fundamental aspect of ligand recognition by this receptor class.

Neonatal Fc Receptor Expression in Dendritic Cells Mediates Protective Immunity against Colorectal Cancer

Cancers arising in mucosal tissues account for a disproportionately large fraction of malignancies. Immunoglobulin G (IgG) and the neonatal Fc receptor for IgG (FcRn) have an important function in the mucosal immune system that we have now shown extends to the induction of CD8(+) T cell-mediated antitumor immunity. We demonstrate that FcRn within dendritic cells (DCs) was critical for homeostatic activation of mucosal CD8(+) T cells that drove protection against the development of colorectal cancers and lung metastases. FcRn-mediated tumor protection was driven by DCs activation of endogenous tumor-reactive CD8(+) T cells via the cross-presentation of IgG complexed antigens (IgG IC), as well as the induction of cytotoxicity-promoting cytokine secretion, particularly interleukin-12, both of which were independently triggered by the FcRn-IgG IC interaction in murine and human DCs. FcRn thus has a primary role within mucosal tissues in activating local immune responses that are critical for priming efficient anti-tumor immunosurveillance.

Interleukin-15 enhances rituximab-dependent cytotoxicity against chronic lymphocytic leukemia cells and overcomes transforming growth factor beta-mediated immunosuppression

Chemoimmunotherapy with anti-CD20 monoclonal antibody rituximab is increasingly used for the treatment of patients with chronic lymphocytic leukemia (CLL). Antibody-dependent cytotoxicity (ADCC) is one of the most important mechanisms of action of rituximab against B-cell malignancies. We studied ways to increase the cytotoxic effect of rituximab on CLL cells by enhancing ADCC. Peripheral blood mononuclear cell (PBMC) or purified natural killer (NK) cells from healthy donors were activated with interleukin-15 (IL-15) and cultured with rituximab-coated CLL cells, and ADCC was evaluated using a (51)chromium release assay. The IL-15 significantly enhanced invitro ADCC against CLL cells, and this effect was mainly mediated by NK cells. The IL-15 treated effector cells with the low affinity FcγRIIIA receptor (158FF) had an ADCC comparable to those with the high affinity FcγRIIIA form (158VF). Inaddition, IL-15 enhanced rituximab-mediated ADCC of CLL cells in the presence of transforming growth factor-beta. The IL-15 increases rituximab-mediated ADCC against CLL, and supports the use of such agents with the goal of improving clinical response to chemoimmunotherapy in patients with CLL.

Cloning and characterization of ovine immunoglobulin G Fc receptor II (FcγRII)

Immunoglobulin G (IgG) Fc receptors (FcγRs) bind to immune complexes through interactions with the Fc region of IgG to initiate or inhibit the defense mechanism of the leukocytes on which they are expressed. In this study, we describe the cloning, sequencing and characterization of ovine FcγRII. By screening a translated expression sequence tag (EST) database with the protein sequence of bovine IgG Fc receptor II, we identified a putative ovine homologue. Using rapid amplification of cDNA ends (RACE), we isolated the cDNA encoding ovine FcγRII from peripheral blood leucocyte RNA. The ovine FcγRII cDNA contains an 894 bp open-reading frame, encoding a 297 amino acid transmembrane glycoprotein composed of two immunoglobulin-like extracellular domains, a transmembrane region and a cytoplasmic tail with an immunoreceptor tyrosine-based inhibitory motif (ITIM). The glycoprotein encoded by the cloned cDNA was then expressed on the surface of COS-7 cells and immunoglobulin-binding assays show that it binds ovine IgG1, but not IgG2. Identification of the ovine FcγRII will aid in the understanding of the molecular basis of IgG–FcγR interaction.

The immunoglobulin-binding Eib proteins from Escherichia coli are receptors for IgG Fc

The immunoglobulin-binding proteins from Eschericia coli (Eibs) comprise a family of six proteins homologous to the Yersinia adhesin YadA. These proteins are postulated to bind to the Fc portion of immunoglobulin G (IgG) in a non-immune manner. However, a recent study [Ghumra, A., Pleass, R.J., 2007. Escherichia coli do not express Fc-receptors for human immunoglobulin G (IgG). Mol. Immunol. 44, 2144–2146] appeared to show that these proteins do not bind Fc and suggested that the binding seen in earlier studies is due to the polyclonal preparations used in the assays containing antibodies specific to epitopes in the Eib proteins. To resolve this matter, we produced purified, recombinant Eibs for the first time and investigated their binding to intact antibodies and Fc fragments by immunoblot and ELISA techniques. We were able to purify four members of the family, EibA, -C, -D and -F, and show conclusively that these bind IgG Fc. We were also able to block the binding of full-length antibody with IgG Fc, but not with IgG Fab. Binding to IgG Fab was not detectable by surface plasmon resonance, whereas the affinities of Eibs to IgG and IgG Fc were in the range of 50–200 nM. We further demonstrate that deglycosylating IgG Fc does not affect Eib binding. Our results show that the Eib proteins do indeed bind human IgG Fc and that IgG Fc receptors are present in E. coli.

Blocking Antibody Access to Neutralizing Domains on Glycoproteins Involved in Entry as a Novel Mechanism of Immune Evasion by Herpes Simplex Virus Type 1 Glycoproteins C and E

Herpes simplex virus type 1 (HSV-1) glycoprotein C (gC) blocks complement activation, and glycoprotein E (gE) interferes with IgG Fc-mediated activities. While evaluating gC- and gE-mediated immune evasion in human immunodeficiency virus (HIV)-HSV-1-coinfected subjects, we noted that antibody alone was more effective at neutralizing a strain with mutations in gC and gE (gC/gE) than a wild-type (WT) virus. This result was unexpected since gC and gE are postulated to interfere with complement-mediated neutralization. We used pooled human immunoglobulin G (IgG) from HIV-negative donors to confirm the results and evaluated mechanisms of the enhanced antibody neutralization. We demonstrated that differences in antibody neutralization cannot be attributed to the concentrations of HSV-1 glycoproteins on the two viruses or to the absence of an IgG Fc receptor on the gC/gE mutant virus or to enhanced neutralization of the mutant virus by antibodies that target only gB, gD, or gH/gL, which are the glycoproteins involved in virus entry. Since sera from HIV-infected subjects and pooled human IgG contain antibodies against multiple glycoproteins, we determined whether differences in neutralization become apparent when antibodies to gB, gD, or gH/gL are used in combination. Neutralization of the gC/gE mutant was greatly increased compared that of WT virus when any two of the antibodies against gB, gD, or gH/gL were used in combination. These results suggest that gC and gE on WT virus provide a shield against neutralizing antibodies that interfere with gB-gD, gB-gH/gL, or gD-gH/gL interactions and that one function of virus neutralization is to prevent interactions between these glycoproteins.

Fcγ Receptor Regulation of Citrobacter rodentium Infection

Citrobacter rodentium, a murine model pathogen for enteropathogenic Escherichia coli, colonizes the colon utilizing attaching and effacing lesions to adhere specifically to the surfaces of intestinal epithelial cells and cause mucosal inflammation. CD4+ T cells, B cells, and immunoglobulin G (IgG), but not secretory IgA or IgM, play a critical role in eradicating this pathogen. Consistent with the importance of IgG in C. rodentium eradication, IgG transport by the neonatal Fc receptor for IgG within the intestinal epithelium also has a critical role in the regulation of C. rodentium infection. It remains to be determined, however, whether Fcgamma receptors (FcgammaRs), the receptors for the Fc portion of IgG, regulate this bacterial infection within mucosal tissues. Therefore, we investigated the roles of FcgammaRs during C. rodentium infection. Fc receptor common gamma chain (FcRgamma)-deficient mice were more susceptible to C. rodentium-induced colitis. This occurred through decreased efficiency of FcR-mediated endocytosis and maturation of dendritic cells and consequently T-cell activation of antigen-specific T cells. Moreover, in the absence of FcgammaRs, phagocytosis by macrophages was significantly diminished. Therefore, activating FcgammaRs play an important role in defending against C. rodentium infection, indicating that the critical role played by IgG in this infection is not mediated by IgG alone but is dependent upon this class of receptors.

Identification and characterization of an alternatively spliced variant of the MHC class I-related porcine neonatal Fc receptor for IgG

The neonatal Fc receptor for immunoglobulin G (IgG) (FcRn) functions to transport maternal IgG to the fetal/neonatal animals and protects IgG from catabolism. The present study identified two pFcRn cDNAs (1.071 and 0.795kb) from intestinal epithelial cells. The corresponding mRNA transcripts were detected in porcine kidney cell line LLC-PK1, peripheral blood mononuclear cells, and porcine tissues by reverse transcription-PCR (RT-PCR) and Northern blot. Sequence analysis showed that the 1.071kb cDNA encodes the full-length pFcRn (pFcRn-L), whereas the 0.795kb cDNA codes for a truncated pFcRn (pFcRn-S) with deletion of 92 amino acids matching the alpha2 domain of pFcRn-L. pFcRn-L was constitutively expressed by epithelial cells; however, pFcRn-S was not detectable in porcine tissues and cell lines although its transcript was abundant. Despite the lack of native pFcRn-S, pFcRn-S was readily detected in transfected cells. Recombinant pFcRn-L was confirmed to bind IgG at pH 6.0, but not at pH 7.5; however, pFcRn-S failed to bind IgG at both pH 5.0-6.0 and 7.5. pFcRn-L was expressed on the cell surface and mainly localized in early endosomes. In contrast, pFcRn-S was absent from cell surface and primarily localized in the lysosome and pFcRn-S trafficking to lysosomes was independent of beta(2)-microglobulin (beta(2)m). The accumulation of pFcRn-S in the lysosome may explain the absence of native pFcRn-S protein expression. In addition, the trafficking of pFcRn-S to the lysosomal compartment suggests that in addition to sorting signals in its cytoplasmic tail, the FcRn structural integrity may be important for proper intracellular trafficking and function.

Affinity and Kinetic Analysis of Fcγ Receptor IIIa (CD16a) Binding to IgG Ligands

Binding of pathogen-bound immunoglobulin G (IgG) to cell surface Fc gamma receptors (FcgammaRs) triggers a wide variety of effector functions. The binding kinetics and affinities of IgG-FcgammaR interactions are hence important parameters for understanding FcgammaR-mediated immune functions. We have measured the kinetic rates and equilibrium dissociation constants of IgG binding to a soluble FcgammaRIIIa fused with Ig Fc (sCD16a) using the surface plasmon resonance technique. sCD16a interacted with monomeric human IgG and its subtypes IgG1 and IgG3 as well as rabbit IgG with on-rates of 6.5 x 10(3), 8.2 x 10(3), 1.1 x 10(4) and 1.8 x 10(4) m(-1) s(-1), off-rates of 4.7 x 10(-3), 5.7 x 10(-3), 5.9 x 10(-3), and 1.9 x 10(-2) s(-1), and equilibrium dissociation constants of 0.72, 0.71, 0.56, and 1.1 mum, respectively. The kinetics and affinities measured by surface plasmon resonance agreed with those obtained from real time flow cytometry and competition inhibition binding experiments using cell surface CD16a. These data add to our understanding of IgG-FcgammaR interactions.

How the controller is controlled – neonatal Fc receptor expression and immunoglobulin G homeostasis

With the discovery of immunoglobulins, immunoglobulin G (IgG) was recognized to possess two unique properties: selective pre- or postnatal transepithelial transport across the placenta in humans or the intestinal epithelium in rodents, respectively, and a prolonged half-life relative to other serum proteins, suggesting protection from catabolism in adults. These observations were noted by Francis Brambell, who further predicted the presence of a saturable receptor responsible for both biological functions. 1 Two decades after these predictions, biochemical and ultimately molecular biological evidence was obtained, in the late 1980s, for the presence of a receptor that was physiologically active in neonatal rodent epithelium. 2,3 However, not until recently with the generation of X-ray crystallographic structures, subsequent structure–function analyses and the creation of a knock-out animal, has it become clear that the so-called neonatal Fc receptor for IgG (FcRn) is responsible for both of the aforementioned functional attributes of IgG physiology: its transport across the neonatal epithelium of rodents and the avoidance of catabolism. 4–8 FcRn consists of a glycosylated heavy chain that is closely related to major histocompatibility complex (MHC) class I molecules in non-covalent association with b2microglobulin (b2m). 9 FcRn binds IgG in a strictly pH

Divergent Immunoglobulin G Subclass Activity Through Selective Fc Receptor Binding

Subclasses of immunoglobulin G (IgG) display substantial differences in their ability to mediate effector responses, contributing to variable activity of antibodies against microbes and tumors. We demonstrate that the mechanism underlying this long-standing observation of subclass dominance in function is provided by the differential affinities of IgG subclasses for specific activating IgG Fc receptors compared with their affinities for the inhibitory IgG Fc receptor. The significant differences in the ratios of activating-to-inhibitory receptor binding predicted the in vivo activity. We suggest that these highly predictable functions assigned by Fc binding will be an important consideration in the design of therapeutic antibodies and vaccines.

Human immunoglobulin G (IgG) Fc receptor IIA (CD32) polymorphism and IgG2-mediated bacterial phagocytosis by neutrophils

Human immunoglobulin G (IgG) Fc receptor IIa (Fc gamma RIIa; CD32) is expressed on phagocytes, triggers phagocytosis, and represents the sole Fc receptor for IgG (Fc gamma R) capable of interaction with IgG2, the main IgG subclass induced in response to bacterial capsular polysaccharides. The two genetically determined structurally different allotypes of human Fc gamma RIIa, the products of the Fc gamma RIIa-R131 and IIa-H131 alleles, have functionally different reactivities with human IgG2. In humans, the Fc gamma RIIa-H131 allotype is known to interact efficiently with complexed human IgG2, whereas the IIa-H131 allotype does so only poorly. This polymorphism may therefore have implications for IgG2-mediated phagocytosis of encapsulated bacteria and susceptibility to bacterial infections. Phagocytosis of IgG2-opsonized bacteria by homozygous Fc gamma RIIa-R/R131, heterozygous IIa-H/R131, and homozygous IIa-H/H131 polymorphonuclear cells (PMN) was compared. A higher phagocytic capacity of IgG2-opsonized group B type III streptococci by PMN of homozygous H/H131 individuals compared with PMN from homozygous R/R131 individuals was observed (P = 0.001), while heterozygous IIa-H/R131 PMN showed intermediate phagocytosis. In this model system, IgG2-mediated phagocytosis was independent of the Fc gamma RIIIb-NA1/NA2 allelic polymorphism.

Human placental Fc receptors

Human immunoglobulin G (IgG) Fc receptors are important in the materno-fetal relationship. Three classes of IgG Fc receptors are recognized which generate multiple isoforms, most of which are expressed in different cellular components of human placenta at different times during pregnancy. Although the distinct biological functions of Fc gamma R phenotypes expressed in human placenta are still unknown, recent data provide evidence for an important association between the Fc gamma R phenotype and transcytosis of IgG in the placenta. Selective transfer of maternal IgG across the placenta provides passive immunity to the fetus during the period when its own immune system is gaining protective potential. Furthermore, placenta-specific macrophages may contribute through Fc gamma R-mediated phagocytosis to the protection of the fetus from either infection or maternal immune attack against paternally inherited fetal antigens. Ontogeny and expression of various isoforms of Fc gamma R subtypes may be the key to the elucidation of the transport mechanism of maternal IgG to the fetus, in addition to the determination of the mechanisms of placental protection of the fetus against the maternal immune system.

Herpes simplex virus glycoproteins E and I facilitate cell-to-cell spread in vivo and across junctions of cultured cells

Herpes simplex virus (HSV) glycoproteins E and I (gE and gI) can act as a receptor for the Fc domain of immunoglobulin G (IgG). To examine the role of HSV IgG Fc receptor in viral pathogenesis, rabbits and mice were infected by the corneal route with HSV gE- or gI- mutants. Wild-type HSV-1 produced large dendritic lesions in the corneal epithelium and subsequent stromal disease leading to viral encephalitis, whereas gE- and gI- mutant viruses produced microscopic punctate or small dendritic lesions in the epithelium and no corneal disease or encephalitis. These differences were not related to the ability of the gE-gI oligomer to bind IgG because the differences were observed before the appearance of anti-HSV IgG and in mice, in which IgG binds to the Fc receptor poorly or not at all. Mutant viruses produced small plaques on monolayers of normal human fibroblasts and epithelial cells. Replication of gE- and gI- mutant viruses in human fibroblasts were normal, and the rates of entry of mutant and wild-type viruses into fibroblasts were similar; however, spread of gE- and gI- mutant viruses from cell to cell was significantly slower than that of wild-type HSV-1. In experiments in which fibroblast monolayers were infected with low multiplicities of virus and multiple rounds of infection occurred, the presence of neutralizing antibodies in the culture medium caused the yields of mutant viruses to drop dramatically, whereas there was a lesser effect on the production of wild-type HSV. It appears that cell-to-cell transmission of wild-type HSV-1 occurs by at least two mechanisms: (i) release of virus from cells and entry of extracellular virus into a neighboring cell and (ii) transfer of virus across cell junctions in a manner resistant to neutralizing antibodies. Our results suggest that gE- and gI- mutants are defective in the latter mechanism of spread, suggesting the possibility that the gE-gI complex facilitates virus transfer across cell junctions, a mode of spread which may predominate in some tissues. It is ironic that the gE-gI complex, usually considered an IgG Fc receptor, may, through its ability to mediate cell-to-cell spread, actually protect HSV from IgG in a manner different than previously thought.

Cytoplasmic domain heterogeneity and functions of IgG Fc receptors in B lymphocytes.

B lymphocytes and macrophages express closely related immunoglobulin G (IgG) Fc receptors (Fc gamma RII) that differ only in the structures of their cytoplasmic domains. Because of cell type-specific alternative messenger RNA splicing, B-cell Fc gamma RII contains an insertion of 47 amino acids that participates in determining receptor function in these cells. Transfection of an Fc gamma RII-negative B-cell line with complementary DNA's encoding the two splice products and various receptor mutants indicated that the insertion was responsible for preventing both Fc gamma RII-mediated endocytosis and Fc gamma RII-mediated antigen presentation. The insertion was not required for Fc gamma RII to modulate surface immunoglobulin-triggered B-cell activation. Instead, regulation of activation involved a region of the cytoplasmic domain common to both the lymphocyte and macrophage receptor isoforms. In contrast, the insertion did contribute to the formation of caps in response to receptor cross-linking, consistent with suggestions that the lymphocyte but not macrophage form of the receptor can associate with the detergent-insoluble cytoskeleton.

Membrane Anchoring of a Human IgG Fc Receptor (CD16) Determined by a Single Amino Acid

CD16 is a low-affinity immunoglobulin G (IgG) Fc receptor that is expressed on natural killer (NK) cells, granulocytes, activated macrophages, and some T lymphocytes. Two similar genes, CD16-I and CD16-II, encode membrane glycoproteins that are anchored by phosphatidylinositol (PI)-glycan and transmembrane polypeptides, respectively. The primary structural requirements for PI-linkage were examined by constructing a series of hybrid cDNA molecules. Although both cDNA's have an identical COOH-terminal hydrophobic segment, CD16-I has Ser203 whereas CD16-II has Phe203. Conversion of Phe to Ser in CD16-II permits expression of a PI-glycan-anchored glycoprotein, whereas conversion of Ser to Phe in CD16-I prevents PI-glycan linkage.

Interferon-gamma (IFN-gamma) as in vitro enhancing factor of peritoneal macrophage defective bactericidal activity during continuous ambulatory peritoneal dialysis (CAPD).

Interferon-gamma (IFN-gamma) can be considered a primary factor required in vitro and in vivo for inducing endocellular lysis of microorganisms by peritoneal macrophages (PM luminal diameter), an essential activity in continuous ambulatory peritoneal dialysis (CAPD) patients that prevents bacterial peritonitis. In 22 uremic patients treated with CAPD we analyzed: (1) the amount of IFN-gamma released by elicited peritoneal lymphocytes (PL); (2) oxidative metabolism and microbicidal activity by elicited PM luminal diameter; (3) immunoglobulin G (IgG) Fc-receptor expression on PM luminal diameter membrane; (4) the effect on PM luminal diameter hydrogen peroxide (H2O2) generation, bactericidal activity, and IgG Fc-receptor expression exerted in vitro by human recombinant IFN-gamma (rIFN-gamma). Results demonstrate that IFN-gamma release by elicited PL is lower in some CAPD patients with high peritonitis incidence (HPI) than in healthy donors or in CAPD patients with low peritonitis incidence (LPI). Simultaneously, PM luminal diameter from CAPD patients with HPI are characterized by a decreased ability to generate oxygen metabolites, to kill bacteria, and by a lack in IgG Fc-receptor expression; these defects were completely cured after being treated with rIFN-gamma. These results show that the IFN-gamma treatment in vitro could strengthen PM luminal diameter phagocytosis, oxygen metabolite generation, and bacterial killing in CAPD patients with HPI, and suggest that IFN-gamma may be considered a possible therapy in vivo for these patients.