bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circulating CD2+ Monocytes Are Dendritic Cells
Authors: Crawford Keith , Gabuzda Dana , Pantazopoulos Vassilios , Xu Jianhua , Clement Chris , Reinherz Ellis , Alper Chester A. 
Published: January 2023

Abstract
Low levels of CD2 have been described on subsets of monocytes, macrophages, and dendritic cells. CD2 is expressed on about one-third of circulating monocytes, at levels one-half log lower than on T or NK cells, representing 2–4% of PBMC. FACS analysis of CD2+ and CD2− monocytes revealed no significant difference in the expression of adhesion molecules (CD11a/b/c), class II Ags (HLA-DR, -DQ, -DP), myeloid Ags (CD13, CD14, CD33), or costimulatory molecules (CD80, CD86). Freshly isolated CD2+ and CD2− monocytes were morphologically indistinguishable by phase contrast microscopy. However, scanning electron microscopy revealed large prominent ruffles on CD2+ monocytes in contrast to small knob-like projections on CD2− monocytes. After 2 days of culture, the CD2+ monocytes largely lost CD14 expression and developed distinct dendrites, whereas the CD2− monocytes retained surface CD14 and remained round or oval. Freshly isolated CD2+ monocytes were more potent inducers of the allogeneic MLR and more efficiently induced proliferation of naive T cells in the presence of HIV-1 gp120 than did CD2− monocytes. After culture in the presence of GM/CSF and IL-4, CD2+ monocytes were up to 40-fold more potent than monocyte-derived dendritic cells or CD2− monocytes at inducing allogeneic T cell proliferation. These findings suggest that circulating CD2+ and CD2− monocytes are dendritic cells and the precursors of macrophages, respectively. Thus, dendritic cells are far more abundant in the blood than previously thought, and they and precursors of macrophages exist in the circulation as phenotypically, morphologically, and functionally distinct monocyte populations.
The CXC Chemokine Stromal Cell-Derived Factor Activates a Gi-Coupled Phosphoinositide 3-Kinase in T Lymphocytes
Authors: Sotsios Yannis , Whittaker Gillian C. , Westwick John , Ward Stephen G. 
Published: January 2023

AbstractThe cellular effects of stromal cell-derived factor-1 (SDF-1) are mediated primarily by binding to the CXC chemokine receptor-4. We report in this study that SDF-1 and its peptide analogues induce a concentration- and time-dependent accumulation of phosphatidylinositol-(3,4,5)-trisphosphate (PtdIns(3,4,5)P3) in Jurkat cells. This SDF-1-stimulated generation of D-3 phosphoinositide lipids was inhibited by pretreatment of the cells with an SDF-1 peptide antagonist or an anti-CXCR4 Ab. In addition, the phosphoinositide 3 (PI 3)-kinase inhibitors wortmannin and LY294002, as well as the Gi protein inhibitor pertussis toxin, also inhibited the SDF-1-stimulated accumulation of PtdIns(3,4,5)P3. The effects of SDF-1 on D-3 phosphoinositide lipid accumulation correlated well with activation of the known PI 3-kinase effector protein kinase B, which was also inhibited by wortmannin and pertussis toxin. Concentrations of PI 3-kinase inhibitors, sufficient to inhibit PtdIns(3,4,5)P3 accumulation, also inhibited chemotaxis of Jurkat and peripheral blood-derived T lymphocytes in response to SDF-1. In contrast, SDF-1-stimulated actin polymerization was only partially inhibited by PI 3-kinase inhibitors, suggesting that while chemotaxis is fully dependent on PI 3-kinase activation, actin polymerization requires additional biochemical inputs. Finally, SDF-1-stimulated extracellular signal-related kinase (ERK)-1/2 mitogen-activated protein kinase activation was inhibited by PI 3-kinase inhibitors. In addition, the mitogen-activated protein/ERK kinase inhibitor PD098059 partially attenuated chemotaxis in response to SDF-1. Hence, it appears that ERK1/2 activation is dependent on PI 3-kinase activation, and both biochemical events are involved in the regulation of SDF-1-stimulated chemotaxis.
Irradiation-Induced Rescue of Thymocyte Differentiation and V(D)J Recombination in Mice Lacking the Catalytic Subunit of DNA-Dependent Protein Kinase
Authors: Wang Chiyu , Bogue Molly A. , Nguyen Anthony P. , Roth David B. 
Published: January 2023

Abstract
Scid mice express a truncated form of the catalytic subunit of the DNA-dependent protein kinase (DNA-PKcs) and are unable to properly rearrange their Ig and TCR genes, resulting in a severe combined immunodeficiency that is characterized by arrested differentiation of B and T lymphocytes. Treatment of scid mice with low doses of gamma irradiation rescues rearrangements at several TCR loci and promotes limited thymocyte differentiation. The machinery responsible for sensing DNA damage and the mechanism by which irradiation compensates for the scid defect in TCR recombination remain unknown. Because DNA-PKcs is present in scid thymocytes, it may mediate some or all of the irradiation effects. To test this hypothesis, we examined the effects of irradiation on DNA-PKcs-deficient (slip) mice. Our data provide the first evidence that DNA-PKcs is not required for limited rescue of thymocyte differentiation or TCR rearrangements.
Activation of CD40 Favors the Growth and Vascularization of Kaposi’s Sarcoma
Authors: Biancone Luigi , Cantaluppi Vincenzo , Boccellino Mariarosaria , Del Sorbo Lorenzo , Russo Simona , Albini Adriana , Stamenkovic Ivan , Camussi Giovanni 
Published: January 2023

Abstract
Although CD40 is expressed by several tumor lines and is up-regulated in tumor vascular endothelium, its role in tumor biology is still unclear. In the present study, we investigated the role of CD40 in the growth and vascularization of Kaposi’s sarcoma (KS). In vitro, stimulation of CD40 induced migration of KS cells and inhibited vincristine-induced apoptosis. Similarly, the CD40 engagement on endothelial cells resulted in cell contraction, migration, and prevention of serum withdrawal-apoptosis. To understand the biological relevance of CD40 in vivo, KS cells were engineered to express and release a soluble form of CD40 (KS-sCD40) able to disrupt CD40-CD154 interaction. SCID mice s.c. injected with KS-sCD40 cells developed tumors that were significantly smaller than those induced by control cells (KS-neo). In addition, KS-sCD40 tumors showed several areas of necrosis, diffuse presence of apoptotic cells, and poor vascularization. In contrast, KS-neo tumors showed few or absent areas of necrosis and apoptosis and intense vascularization. Moreover, anti-CD40 Abs stimulated neo-angiogenesis in a murine model in which s.c. implantation of Matrigel was used as a vehicle for the delivery of mediators. These observations provide demonstration that CD40 supports tumor cell survival, growth, and neo-vascularization of KS.
Engagement of α4β7 Integrins by Monoclonal Antibodies or Ligands Enhances Survival of Human Eosinophils In Vitro
Authors: Meerschaert JoAnn , Vrtis Rose F. , Shikama Yusuke , Sedgwick Julie B. , Busse William W. , Mosher Deane F. 
Published: January 2023

AbstractAsthma is characterized by an airway inflammatory infiltrate that is rich in eosinophilic leukocytes. Cellular fibronectin and VCAM-1, ligands for α4 integrins, are enriched in the fluid of airways of allergic patients subjected to Ag challenge. We therefore hypothesized that ligands of α4 integrins can promote eosinophil survival independent of cell adhesion. Cellular fibronectin and VCAM-1 increased viability of human peripheral blood eosinophil in a dose- and time-dependant manner whether the ligand was coated on the culture well or added to the medium at the beginning of the assay. Eosinophils cultured with cellular fibronectin were not adherent to the bottom of culture wells after 3 days. Treatment with mAb Fib 30 to β7, but not mAb P4C10 or TS2/16 to β1, increased eosinophil survival. The increased survival of eosinophils incubated with Fib 30 was blocked by Fab fragments of another anti-β7 mAb, Fib 504. Eosinophils incubated with soluble cellular fibronectin or mAb Fib 30 for 6 h demonstrated a higher level of GM-CSF mRNA than eosinophils incubated with medium alone. Addition of neutralizing mAb to GM-CSF during incubation, but not mAbs to IL-3 or IL-5, reduced the enhancement of eosinophil survival by soluble cellular fibronectin or mAb Fib 30 to control levels. Thus, viability of eosinophils incubated with cellular fibronectin or VCAM-1 is due to engagement, probably followed by cross-linking, of α4β7 by soluble ligand (or mAb) that stimulates autocrine production of GM-CSF and promotes eosinophil survival.
On Isoagglutinin Reactions of Human Blood Other Than Those Defining the Blood Groups
Authors: Landsteiner K. , Levine Philip 
Published: January 2023

Summary
A study was undertaken on the occurrence of atypical isoagglutinin reactions of human blood. Such a technic was purposely chosen as would detect sera of even slight activity. In this way rather numerous irregular reactions were found in a material obtained from patients with mental diseases.
Most of the reactions observed may be put under the heading of cold agglutination, that is, the sera are active only at low temperature and give very weak agglutination at room temperature (20°). A smaller number of sera (about 3 per cent) contained agglutinins of a type intermediate between cold agglutinins and typical isoagglutinins since their reactions were distinctly noticeable also under the usual conditions of blood grouping. In all of the cases with atypically reacting sera the blood cells showed no abnormal behavior and could readily be grouped. Also the grouping of the sera was not interfered with by the presence of the irregular agglutinins. Hence the irregularities are superimposed upon the much more prominent group properties, and are not in conflict with the scheme of the four blood groups, the usefulness of which cannot be questioned (cf. Thomsen (18)).
With regard to the practice of transfusions, it may be stated that in several instances in which the serum of the recipient contained irregular agglutinins for the blood of the donor no untoward symptoms at all were observed.
Several sera of groups O, A, and B, described, had agglutinins which were similar with regard to their specificity.
In groups A and AB two types of agglutinins were found specific in general for cells of one or the other subgroup of group A; those agglutinating blood AA2 showed in addition a specific action on cells of group O (cf. Schiff (30)). The properties of these sera demonstrate again quite definitely the existence of subgroups in group A, a distinction hardly significant at present for practical purposes.
The results with the abnormal agglutinins of human sera give further support to the conclusion that there exists a great number of individual differences of human blood.
Virolysis of complement-resistant HIV-1 by antibodies in the plasmas from HIV-1-infected individuals (128.10)
Authors: Yu Qigui , Shikuma Cecilia , Shiramizu Bruce , Hu Ningjie 
Published: January 2023

Abstract
Background: Ab responses to HIV-1 Ags are generally vigorous at all stages of viral infection, but fail to contain viral replication through Ab-dependent complement-mediated virolysis (ADCMV). Human CD59, an inhibitor of the membrane-attack complex formation of complement on the surface of HIV-1 virions, provides viral resistance to ADCMV. Objective: to abrogate CD59 function for enhancing HIV-1 virolysis by Abs in plasma of HIV-1-infected individuals. Method: HIV-1 virions were pretreated with anti-human CD59 Ab, and then tested for sensitivity to ADCMV in the presence of plasma from HIV-1-infected individuals. Virolysis (%) was calculated by measuring the release of p24 from HIV-1 virions caused by complement activation compared to total p24 released by detergent. Results: HIV-1 virions prepared from OM10 cells, which express high levels of CD59, were resistant to ADCMV, but became sensitive to ADCMV when the virions were pretreated with anti-human CD59 Ab. In total, 16 plasma samples from different HIV-1-infected individuals at acute or chronic stages of infection were tested and the average % of virolysis was 32.7 % with blocking of CD59 function, which is significantly greater than the average % of virolysis without blocking of CD59 function (4.9%) (p&lt;0.001). Conclusions: abrogating CD59 function could enhance HIV-1 virolysis by Abs in the plasmas from HIV-1-infected individuals.
Alloferon inhibits the activation of Kaposi's sarcoma-associated herpesvirus through suppression of nuclear factor-kappa B (NF-kB) activation (128.14)
Authors: Lee Na Eun , Kang Jae Seung , Kong Joo Myoung , Bae Se Yeon , Kim Hye Min , Maeng Hyung Gun , Hwang Young Il , Lee Wang Jae 
Published: January 2023

Abstract
Kaposi's sarcoma-associated herpesvirus (KSHV) is a human oncogenic herpesvirus that causes Kaposi's sarcoma and primary effusion lymphoma. KSHV maintains a latent phase in infected cells but undergoes lytic reactivation in response to various stimuli. Alloferon is an immunomodulating peptide originating from an insect which has been used clinically as antiviral drug in Russia and showed remarkable effect on the prevention of recurrent herpesvirus infections. However, its specific mechanism still remains unknown. The effects of alloferon on the regulation of viral activation and its specific mechanism in virus-infected cells are investigated. In this study, BCBL-1, a persistent KSHV-infected B lymphoma cell line is used, which is reactivated to lytic cycle by TPA treatment. The results tell that alloferon effectively suppressed the down-regulation of cell proliferation induced by TPA treatment, implying that the KSHV reactivation within BCBL-1 can be regulated by alloferon. The results showed that alloferon decreased the expression level of KSHV viral proteins, such as RTA, ORF45 and vIRF2. Furthermore, alloferon suppressed the increase of calcium influx in store-operated calcium entry (SOCE) induced by TPA treatment, which led us to investigate whether alloferon can regulate nuclear factor-kappa B (NF-kB) activity in BCBL-1, since NF-kB is activated by viral infection as well as by calcium influx in immune cells. NF-kB activation in BCBL-1 was effectively inhibited by alloferon. Taken together, it is suggested that alloferon might be used as an effective antiviral agent on KSHV infection through the down-regulation of NF-kB activity.
High levels of chronic immune activation in both CD8 and CD4 T cell compartments negatively influences HCV treatment outcome in HCV/HIV-1 co-infection (128.17)
Authors: Gonzalez Veronica D , Falconer Karolin , Blom Kim G , Reichard Olle , Weis Nina , Alaeus Annette , Sandberg Johan K 
Published: January 2023

Abstract
Chronic immune activation is strongly associated with Human Immunodeficiency virus 1 (HIV-1) disease progression. Here, we have investigated the state of T cell immune activation, as well as T cell responses to hepatitis C virus (HCV), in patients with HCV/HIV-1 co-infection on effective anti-retroviral therapy (ART). Co-infected subjects displayed elevated immune activation as determined by CD38 expression in both CD4 and CD8 T cells, as compared to mono-infected control groups. HCV-specific T cells in response to HCV antigens tended to be stronger in the co-infected patients with a more pronounced IFNγ profile by CD8 T cells and this group also had higher HCV loads at baseline. Patients who reached a sustained virological response to peg-interferon-α and ribavirin treatment displayed significantly lower pre-treatment levels of chronic T cell activation and a trend towards stronger HCV-specific T cell responses, as compared to patients who failed to clear. Data suggest a link between high levels of chronic immune activation, poor adaptive immune responses and HCV treatment failure in HCV/HIV-1 co-infected subjects. We suggest that the high level of chronic immune activation may provide a clue as to why patients co-infected with these viruses in general display faster viral disease progression.
This work was supported by the Swedish Research Council, SIDA and the Swedish National Board of Health and Welfare.
Cytokines and Chemokines Induced by Human Herpesvirus-8 Infection in Myeloid Dendritic Cells and B Cells (128.27)
Authors: Knowlton Emilee , Rappocciolo Giovanna , Piazza Paolo , Jenkins Frank , Jais Mariel , Rinaldo Charles 
Published: January 2023

Abstract
Objectives: Myeloid dendritic cells (DC) and B cells are professional antigen presenting cells (APC) susceptible to HHV-8 infection after DC-SIGN receptor binding. However, the virus elicits productive infection in B cells but not in DC. We examined if these different virus pathways were related to differential cytokine and chemokine production.
Methods: DC and B cells were loaded with purified HHV-8, UV-inactivated HHV-8 and/or endotoxin. Supernatants were examined for cytokines and chemokines from 0 to 48h post-infection by Cytometric Bead Array (BD).
Results: Peak levels of TNF-α, IL-6, IL-8, IL-10, MIP-1α and MIP-1β of 52 (IL-10) to 4.4 x 104 (MIP-1β) pg/ml were detected in B cell cultures by 24-48h of HHV-8 infection, which were 3.5 to 52.5 fold higher than in uninfected B cell cultures. In contrast, DC produced peak amounts of IP-10, MCP-1, RANTES, MIP-1α and MIP-1β of 19 (IP-10) to 1.5 x 104 (MIP-1β) pg/ml by 24-48h, which were 1.5-10 fold higher than in uninfected DC. HHV-8 and UV-inactivated HHV-8 suppressed production of IL-12p70 in endotoxin treated DC. Furthermore, UV inactivation diminished cytokine/chemokine production in B cells but not DC.
Conclusions: Elevated levels of several inflammatory cytokines and MIP chemokines were detected in HHV-8 infected B cells. In contrast, HHV-8 and UV-inactivated HHV-8 loaded DC produced MIP chemokines MCP-1 and IP-10, but not IL-12 p70. Distinct cytokine production by HHV-8 infected B cells and DC could play a role in viral replication in, and function of, these APC.
(RO1 CA82053,U01 AI35041)
Aged-associated resistance to viral disease correlates with decreased recruitment of mature NK cells to the lymph node draining the site of viral infection and not with defective adaptive immunity (128.31)
Authors: Fang Min , Sigal Luis 
Published: January 2023

Abstract
Ectromelia virus (ECTV) is an Orthopoxvirus that causes mousepox, the murine equivalent of human smallpox. The mice strains can be divided into resistant and susceptible stains. C57BL/6 (B6) mice are naturally resistant to mousepox due to the collaborative interaction of innate and adaptive immune responses. However, we have found that starting at 8 months of age, B6 mice gradually lost their natural resistance to mousepox and frequently die 7-10 days post infection (PI). Compared with young mice, aged mice had highly increased virus loads in central organs and severely reduced T cell responses at 7 day PI. Yet, the defect was not T cell intrinsic because when adoptively transferred into young mice, the T cells from aged mice responded to infection as the youngs. Further analysis showed that as compared to young mice, the virus loads in the central organs of aged mice were significantly increased at 3 days PI, a time when the T cell responses were undetectable. Together, these suggested that the susceptibility of aged mice was due to decreased innate rather than adaptive immunity. We have recently shown NK cells control the early spread of virus from the D-LN to central organs. Therefore, we next focused on this cell population. We found that the LNs of naïve aged mice have a reduced proportion of NK cells which is particularly accentuated for the mature (CD27-, CD11b+) population. Furthermore, following viral infection, the recruitment of mature NK cells to the draining LN of aged mice was impaired. Together our data suggests that a defect in the homing of mature NK cells to the LN result in uncontrolled early viral replication and dissemination. Our data sheds new light to our understanding for why older individuals are more susceptible to viral disease.
This work is supported by NIH grant R21AI077021 to LJS
Lack of oviduct pathology in mice infected with TLR2-signaling deficient chlamydiae is associated with earlier resolution of oviduct inflammation, and a decreased Th17 response (129.10)
Authors: Darville Toni , Frazer Lauren , Scurlock Amy M , Chandra-Kuntal Kumar , O'Connell Catherine 
Published: January 2023

Abstract
TLR2 KO mice infected with wild-type C. muridarum strain Nigg and immunologically normal mice infected with plasmid-deficient C. muridarum CM3.1, that fails to activate TLR2, are protected from oviduct pathology during primary and challenge infection. Genital tracts harvested from normal mice sacrificed 7, 14, 21, and 28 days post infection with Nigg or CM3.1 were examined histologically. On day 14, neutrophil infiltrates were significantly decreased in the oviducts from mice infected with CM3.1 versus oviducts from mice infected with Nigg. On days 21 and 28, neutrophils and lymphocytes were significantly decreased in oviducts of mice infected with CM3.1 versus Nigg. Quantitative culture of oviduct homogenates thru 35 days post infection revealed equivalent bacterial burden and resolution of infection in both groups by day 19. Significant amounts of TNF, IL-1α, IL-1β, IL-6, GM-CSF, G-CSF, MIP-2, KC and IFN-γ were detected by bead assay in the oviduct homogenates of Nigg-infected mice on days 9 through 15, but were low or undetectable in mice infected with CM3.1. ELISPOT for IFN-γ and IL-17 producing CD4 T cells in iliac nodes reveal significantly increased Th17 cells on days 7 and 20 post infection in Nigg-infected mice. Chlamydial-induced TLR2 signaling promotes enhanced cytokine production, prolonged oviduct inflammation, and activation of Th17 cells that may contribute to induction of pathology.
Enhanced severity of malaria infection in simian immunodeficiency virus (SIV) infected rhesus macaques (129.15)
Authors: Trott Kristin A , Chau Jennifer Y , Luckhart Shirley , Abel Kristina 
Published: January 2023

Abstract
Epidemic HIV and malaria co-occur in Africa and Asia. We developed a rhesus macaque model of SIV and Plasmodium fragile infection to model human co-infection. From available human data, we hypothesized that P. fragile infection during acute SIV infection enhances immune activation and thereby virus replication and, conversely, that SIV infection enhances parasitemia and parasite transmission in co-infected macaques.
Immunological, parasitological and virological parameters were assessed throughout the course of infection by multiparameter flow cytometry, blood smears, and PCR.
P. fragile-only infection resulted in increased CCR5 and Ki67 expressing CD4+ T cells, potential target cells of SIV, during peak parasitemia. Indeed, acute malaria infection was associated with increased viremia in co-infected animals. Further, SIV-induced immunosuppression was correlated with severe anemia and uncontrolled parasitemia in co-infected animals. Importantly, oocyst numbers in mosquitoes that fed on blood from co-infected animals were higher than those that fed on blood from P. fragile only infected animals. These data suggest that co-infection increases the rate of transmission of both SIV and malaria in co-infected animals.
Our model can be used to elucidate the mechanisms that underlie increased transmission and altered immunity during HIV-P. falciparum co-infection in humans and to test new therapies.
NIH IR21AI077373, T32 AMID, STAR, VSTP