scholarly journals Edible Oxya chinensis sinuosa—Derived Protein as a Potential Nutraceutical for Anticancer Immunity Improvement

Nutrients ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3236
Author(s):  
Woo Sik Kim ◽  
Jeong Moo Han ◽  
Ha-Yeon Song ◽  
Eui-Hong Byun ◽  
Ho Seong Seo ◽  
...  
Keyword(s):  
T Cells ◽  
Colon Carcinoma ◽  
T Cell Response ◽  
Mitogen Activated Protein Kinase ◽  
Type I ◽  
Antigen Uptake ◽  
Surface Molecules ◽  
Ifn Γ ◽  
Anticancer Immunity

Oxya chinensis sinuosa (Ocs) is consumed as representative edible insects in Asia, but its function in various immune systems remains unclear. This study aimed to demonstrate the immunomodulatory effect, particularly on the innate and adaptive immune response, of Ocs protein (Ocs-P) and to investigate its function as a potent anticancer immunostimulant when administered during the progression stage of colon carcinoma in tumor-bearing mice. Our in vitro results demonstrated that Ocs-P treatment induces phenotypic alteration (increased expression of surface molecules and production of T Helper type I-polarizing (Th1-polarizing) cytokines and decreased antigen uptake ability) of dendritic cells (DCs) through the activation of Mitogen-activated protein kinase (MAPK) and nuclear factor kappa B-dependent (NF-κB-dependent) signaling pathways. Additionally, Ocs-P-stimulated DCs initiated differentiation of naive T cells into IFN-γ-producing Th1-type T cells effectively and activated cytotoxic CD8+ T cell response. In colon carcinoma-bearing mouse models, oral administration of Ocs-P inhibited tumor growth and restored the expression of decreased surface molecules in lineage-CD11c+MHC-II+ splenic DCs. Furthermore, Ocs-P administration enhanced the generation of multifunctional CD4+ and CD8+ T cells expressing Th1-type cytokines (TNF-α, IFN-γ, and IL-2) and the degranulation marker (CD107a). Collectively, these results suggest that Ocs-P demonstrates an immunostimulatory effect and may induce powerful anticancer immunity.

scholarly journals BHLHE40 Regulates IL-10 and IFN-γ Production in T Cells but Does Not Interfere With Human Type 1 Regulatory T Cell Differentiation

2021 ◽  
Vol 12 ◽  
Author(s):  
Molly Javier Uyeda ◽  
Robert A. Freeborn ◽  
Brandon Cieniewicz ◽  
Rosa Romano ◽  
Ping (Pauline) Chen ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Differentiation ◽  
Ex Vivo ◽  
Surface Expression ◽  
Surface Molecules ◽  
Ifn Γ ◽  
And Function ◽  
Tr1 Cells

Type 1 regulatory T (Tr1) cells are subset of peripherally induced antigen-specific regulatory T cells. IL-10 signaling has been shown to be indispensable for polarization and function of Tr1 cells. However, the transcriptional machinery underlying human Tr1 cell differentiation and function is not yet elucidated. To this end, we performed RNA sequencing on ex vivo human CD49b+LAG3+ Tr1 cells. We identified the transcription factor, BHLHE40, to be highly expressed in Tr1 cells. Even though Tr1 cells characteristically produce high levels of IL-10, we found that BHLHE40 represses IL-10 and increases IFN-γ secretion in naïve CD4+ T cells. Through CRISPR/Cas9-mediated knockout, we determined that IL10 significantly increased in the sgBHLHE40-edited cells and BHLHE40 is dispensable for naïve CD4+ T cells to differentiate into Tr1 cells in vitro. Interestingly, BHLHE40 overexpression induces the surface expression of CD49b and LAG3, co-expressed surface molecules attributed to Tr1 cells, but promotes IFN-γ production. Our findings uncover a novel mechanism whereby BHLHE40 acts as a regulator of IL-10 and IFN-γ in human CD4+ T cells.

scholarly journals Safety Profile of a Virus-Like Particle-Based Vaccine Targeting Self-Protein Interleukin-5 in Horses

Vaccines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 213 ◽  
Author(s):  
Sigridur Jonsdottir ◽  
Victoria Fettelschoss ◽  
Florian Olomski ◽  
Stephanie C. Talker ◽  
Jelena Mirkovitch ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cell ◽  
Mononuclear Cells ◽  
Clinical Signs ◽  
T Cell Response ◽  
Type I ◽  
Cell Responses ◽  
Virus Like Particle ◽  
Ifn Γ

Background: Insect bite hypersensitivity (IBH) is an eosinophilic allergic dermatitis of horses caused by type I/IVb reactions against mainly Culicoides bites. The vaccination of IBH-affected horses with equine IL-5 coupled to the Cucumber mosaic virus-like particle (eIL-5-CuMVTT) induces IL-5-specific auto-antibodies, resulting in a significant reduction in eosinophil levels in blood and clinical signs. Objective: the preclinical and clinical safety of the eIL-5-CuMVTT vaccine. Methods: The B cell responses were assessed by longitudinal measurement of IL-5- and CuMVTT-specific IgG in the serum and plasma of vaccinated and unvaccinated horses. Further, peripheral blood mononuclear cells (PBMCs) from the same horses were re-stimulated in vitro for the proliferation and IFN-γ production of specific T cells. In addition, we evaluated longitudinal kidney and liver parameters and the general blood status. An endogenous protein challenge was performed in murine IL-5-vaccinated mice. Results: The vaccine was well tolerated as assessed by serum and cellular biomarkers and also induced reversible and neutralizing antibody titers in horses and mice. Endogenous IL-5 stimulation was unable to re-induce anti-IL-5 production. The CD4+ T cells of vaccinated horses produced significantly more IFN-γ and showed a stronger proliferation following stimulation with CuMVTT as compared to the unvaccinated controls. Re-stimulation using E. coli-derived proteins induced low levels of IFNγ+CD4+ cells in vaccinated horses; however, no IFN-γ and proliferation were induced following the HEK-eIL-5 re-stimulation. Conclusions: Vaccination using eIL-5-CuMVTT induces a strong B-cell as well as CuMVTT-specific T cell response without the induction of IL-5-specific T cell responses. Hence, B-cell unresponsiveness against self-IL-5 can be bypassed by inducing CuMVTT carrier-specific T cells, making the vaccine a safe therapeutic option for IBH-affected horses.

Cultured Human B Cell APCs Expanded Using Il-4 and CD40 Ligand Preferentially Promote a Type 2 T Cell Response to Alloimmune Stimulation.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2668-2668
Author(s):  
Abdul Tawab ◽  
Yoshiyuki Takahashi ◽  
Childs Richard ◽  
Kurlander J. Roger
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Cell Response ◽  
Cd40 Ligand ◽  
T Cell Response ◽  
Ifn Γ

Abstract In vitro stimulation of human peripheral blood B cells with recombinant IL-4 and CD40 ligand (CD40L) markedly increases their expression of MHC and costimulatory molecules, thus enhancing antigenic peptide presentation to T cells. Because these cells proliferate extensively in vitro (unlike monocytes or dendritic cells), they represent a promising and convenient reagent for the generation and maintenance of antigen-specific T cells for use in a variety of experimental or therapeutic settings. However, the impact of this type of B cell APC on cytokine production by responder T cells has hitherto not been examined. To address this issue, we stimulated normal human T cells with either allogeneic B cells (generated in vitro) or with MNCs obtained from the same donor. After 7 days, T cells were washed and re-challenged with the same APCs. The resulting alloreactive cytokine response was measured using quantitative ELISPOT methods and expressed as the frequencies of IFN-γ, IL-4, and IL-5 producing cells per thousand responder cells added. B cell- and MNC-primed cell lines both produced vigorous lymphokine responses, but B cell-stimulated T cells consistently produced more IL-5 spots (mean of 265 vs. 98/1000 responders, p<0.002) and fewer IFN-γ spots (163 vs 386/1000 cells, p<0.005) than MNC-stimulated cells. Further, the ratio of IFN-γ to IL-5 spots was almost ten-fold lower in B cell-stimulated cultures compared to MNC-induced cultures (0.67 vs. 5.2, p<0.001). ELISPOT studies assessing the ratio of IFN-γ to IL-4 spots and ELISA assays comparing IFN-γ and IL-5 levels from culture supernatants demonstrated the same pattern of marked type 2 skewing by B cells. This pattern was unaffected by the presence of anti-IL-4 antibody suggesting type 2 skewing was not mediated by IL-4. Cytokine skewing produced by B cells or MNC could be partially reversed by swapping MNC and B cells during re-stimulation on day 7, but this plasticity was markedly reduced after 3 (weekly) cycles of B cell or MNC re-stimulation in vitro. Type 2 skewing by B cells was enhanced when monocytes were removed from responder T cell populations by either depleting CD14+ positive cells or by positive selection of T cells prior to stimulation. In contrast, type 2 polarization could be prevented using recombinant IL-12. Not all cells of B-cell origin share the same propensity to type 2 skewing observed with IL-4/CD40L-stimulated B cells; under identical conditions, EBV-transformed B cells stimulated alloimmune T cells to produce a strong type 1 cytokine response comparable to that produced by MNCs. In summary, IL-4/CD40L-stimulated B cells strongly promote a type 2 T cell response during primary alloimmune challenge; this skewing can become fixed after repeated B cell stimulation. Investigators using these cells as APC should be aware of this potential phenomenon, particularly during primary T cell responses. It is also important to consider the factors described above that may exacerbate or ameliorate this effect.

Regulation of alveolar macrophage-T cell interactions during Th1-type sarcoid inflammatory process

1999 ◽  
Vol 277 (2) ◽  
pp. L240-L250 ◽  
Author(s):  
Carlo Agostini ◽  
Livio Trentin ◽  
Alessandra Perin ◽  
Monica Facco ◽  
Marta Siviero ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Costimulatory Molecules ◽  
T Cell Response ◽  
Accessory Function ◽  
B7 Family ◽  
Ifn Γ ◽  
Low Levels ◽  
Antigen Presenting

The accessory function of antigen-presenting cells depends on the presence of a number of costimulatory molecules, including members of the B7 family (CD80 and CD86) and the CD5 coligand CD72. The aim of this study was to evaluate the regulation of T cell-antigen-presenting cell costimulatory pathways in the lung of patients with a typical Th1-type reaction, i.e., sarcoidosis. Although normal alveolar macrophages (AMs) did not bear or bore low levels of costimulatory molecules, AMs from sarcoid patients with CD4 T-cell alveolitis upmodulated CD80, CD86, and CD72 and expressed high levels of interleukin (IL)-15; lymphocytes accounting for T-cell alveolitis expressed Th1-type cytokines [interferon (IFN)-γ and/or IL-2] and bore high levels of CD5 and CD28 but not of CD152 molecules. In vitro stimulation of AMs with Th1-related cytokines (IL-15 and IFN-γ) upregulated the expression of CD80 and CD86 molecules. However, stimulation with IL-15 induced the expression of Th1-type cytokines (IFN-γ) and CD28 on sarcoid T cells, suggesting a role for this macrophage-derived cytokine in the activation of the sarcoid T-cell pool. The hypothesis that CD80 and CD86 molecules regulate the sarcoid T-cell response was confirmed by the evidence that AMs induced a strong proliferation of T cells that was inhibited by pretreatment with CD80 and CD86 monoclonal antibodies. To account for these data, it is proposed that locally released cytokines provide AMs with accessory properties that contribute to the development of sarcoid T-cell alveolitis.

Double Loading of Dendritic Cell MHC Class I and MHC Class II with an AML Antigen Repertoire Enhances Primary and Secondary T-Cell Responses In Vitro.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2529-2529
Author(s):  
William K. Decker ◽  
Dongxia Xing ◽  
Sufang Li ◽  
Simon N. Robinson ◽  
Hong Yang ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mhc Class Ii ◽  
Cd8 T Cells ◽  
Class Ii ◽  
T Cell Response ◽  
Class I ◽  
Cross Presentation ◽  
Ifn Γ

Abstract Despite improvements in therapy for acute myelogenous leukemia (AML), a significant percentage of patients still relapse and succumb to their disease. Dendritic cell immunotherapy offers the promise of potentially effective supportive therapy for a variety of neoplastic conditions; and the use of DCs loaded with tumor antigens is now recognized as an important investigational therapy. Though a variety of methods have been used to load DC vaccines, the loading of the MHC class II compartment with tumor lysate has predominated. The priming of a class II-mediated (CD4) T-cell response may be crucial to the success of DC immunotherapy as such a response is likely required for the development of memory CD8+ T-cells. DC cross-presentation is credited with the ability of lysate-loaded DCs to prime both CD4 and CD8 T-cell responses, enabling the generation of CD8+ CTLs without the loading of the MHC class I compartment (i.e. the cytoplasm). Recently, however, several reports have raised doubts as to the efficiency of cross-presentation as a mechanism for CTL priming in vivo. To examine this issue, we have loaded human DCs with both AML tumor lysate and mRNA. This technique allows the full repertoire of class I antigens to be presented without dependence upon cross-presentation; and, moreover, provides a full complement of class II antigens necessary for CD4 T-cell priming and the generation of memory responses. Methods: CD14+ precursors were isolated from normal donor PBPCs by magnetic separation. Immature DCs were then generated by culturing precursors for six days in GM-CSF and IL-4. Lysate was produced by three successive freeze/thaw cycles of blasts. mRNA was extracted from blasts using Trizol and oligo-dT separation. Immature DCs were pulsed for three hours with AML lysate and subsequently electroporated with AML mRNA. Loaded DCs were matured for 48 hours with IL-1β, TNF-α, IL-6, and PGE2 and then used to prime autologous T-cells. Short-term responses were assayed on day 5 of the 1st stimulation. Memory responses were assayed on day 10 of a tertiary stimulation. Results: Doubly-loaded DCs can prime a superior T-cell response in vitro in comparison to that of singly-loaded DCs, demonstrating a 30–70% increase in IFN-γ ELISpots over lysate-loaded DCs (p&lt;0.001) and a 3–4 fold increase in ELISpots in comparison to mRNA loaded DCs (p&lt;0.001). These results were verified by flow cytometry which showed 35% of CD8+ T-cells primed by doubly-loaded DCs were CD69+/IFN-γ+ vs. 14% of CD8+ T-cells primed by lysate-loaded DCs (p&lt;0.001). This enhancement may be based upon both an upregulation of CD83 surface expression (p&lt;0.0019) of doubly-loaded DCs and/or the upregulation of B7.1/B7.2 that accompanies elevated CD40L signaling. Memory responses were also greatly improved, with a 126% increase in total ELISpots (double loaded DCs versus lysate loaded DCs; p&lt;0.03) and a 187% increase in total IFN-γ secretion (p&lt;0.03). Unloaded (p&lt;0.01) and mRNA (p&lt;0.007) loaded DCs exhibited a virtual inability to generate memory T-cells in vitro, suggesting that the perpetuation of the memory response is reliant upon T-cell help. Conclusion: DCs doubly-loaded with lysate and mRNA are more efficient in the generation of primary and secondary immune responses than are singly-loaded DCs. The clinical administration of such doubly-loaded DCs may offer an important therapeutic option to patients with AML.

Blast Crisis CML Cells Require IFN-γ Conditioning For Effective GVL Whereas Chronic Phase CML Cells Do Not: An Explanation For Chronic Phase CML GVL-Sensitivity

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2013-2013
Author(s):  
Catherine Matte-Martone ◽  
Warren D Shlomchik
Keyword(s):  
T Cells ◽  
Conflicts Of Interest ◽  
Blast Crisis ◽  
Chronic Phase ◽  
Type I ◽  
Mrna Levels ◽  
Cd4 Cells ◽  
Cd8 Cells ◽  
Ifn Γ

Abstract While the GVL effect is potent against chronic phase (CP) CML, it is less effective against blast crisis (BC) CML and AML. To better understand this difference we have been studying GVL against mouse models of CP-CML (mCP-CML) and BC-CML (mBC-CML) induced by infecting bone marrow (BM) with retrovirus encoding bcr-abl alone (mCP-CML) or also with a retrovirus encoding the NUP98-HOXA9 fusion (mBC-CML). We previously reported MHCII-/- mBC-CML and mCP-CML to be completely resistant to CD4-mediated GVL, but the leukemia stem cells (LSCs) of each expressed little if any MHCII. We hypothesized that MHCII might be upregulated in an alloimmune environment. Consistent with this, in mice transplanted with allogeneic T cells, mBC-CML and mCP-CML LSCs upregulated MHCII as well as MHCI and ICAM-1. To test the hypothesis that IFN-γ upregulated LSC MHC post BMT, we created IFN-γR-/- mBC- and mCP-CML. IFN-γR-/- mBC-CML LSCs did not upregulate MHCII, MHCI or ICAM-1 in vivo, whereas they were upregulated on IFN-γR-/- mCP-CML LSCs. Consistent with this, IFN-γR-/- mBC-CML was completely resistant to GVL (C3H.SW→B6) mediated by CD4 or CD8 cells whereas GVL against IFN-γR-/- mCP-CML was equivalent to that against wt mCP-CML. Therefore independence from IFN-γ conditioning is a key property that at least in part explains the sensitivity of mCP-CML to GVL. In contrast, type I IFN receptor-deficient mCP-CML and mBC-CML upregulated MHC and were fully GVL-sensitive. That IFN-γR-/- mBC-CML was resistant to CD8-mediated GVL was surprising given that mBC-CML LSCs are constitutively MHCI+. These data suggest that IFN-γ does more than simply upregulate MHCI. To further explore this we performed gene expression analysis. Illumina arrays revealed that wt mBC-CML and not IFN-γR-/- LSCs from alloimmune mice have higher mRNA levels of death pathway genes Ripk1, Fas, Caspases, 1,2,8, Diablo, Apaf1 and Mdm2 and antigen presentation genes Ciita, Tap1, and proteasome subunit Psmb9, in addition to the canonical IFN-γ-induced gene IRF1. In contrast, c-myc expression was reduced. We next focused on the effects of IFN-γ on mBC-CML LSCs. MHC upregulation did not require that T cells make TCR:MHC interactions as CD8 cells induced upregulation of MHCII in MHCI-/- mBC-CML and CD4 cells induced MHCI upregulation on MHCII-/- mBC-CML. MHCII+ mBC-CML were bona fide LSCs as they transferred mBC-CML, but the resultant leukemias were MHCII-, indicating that MHCII upregulation was dynamic. In vitro IFN-γ led to STAT1 phosphorylation within 15 minutes whereas MHCII upregulation took 24-48 hours. Upregulation could be initiated with an IFN-g pulse as short as 30’ but was maximal with a 24 hour stimulation. Donor T cells were the key source of IFN-γ as IFN-γ-/- T cells failed to induce MHCII upregulation and did not mediate GVL, despite engraftment and expansion. Given that cognate interactions were not required for IFN-γ-induced MHCII upregulation, we tested whether GVL could be augmented by IFN-γ-producing T cells that could not directly kill LSCs. To do so, irradiated B6 mice were reconstituted with BALB/c BM, B6 MHCI- mBC-CML without or with BALB/c T cells as follows: a) wt CD4; b) IFN-γ-/- CD4; c) wt CD4 + wt CD8; or d) IFN-γ-/- CD4 + wt CD8. Despite not being able to interact with MHCI- mBC-CML, wt CD8 rescued LSC MHCII upregulation in recipients of IFN-γ-/- CD4 cells and improved early GVL in recipients of both wt and IFN-γ-/- CD4 cells as measured by the number of mBC-CML cells in spleen, blood and BM on day +14. However, the effect was short-lived as later post transplant mBC-CML LSCs lost MHCII expression, likely due to contraction of IFN-γ-producing T cells, and mice succumbed to mBC-CML. These studies suggest that a requirement for IFN-γ stimulation is a key feature that distinguishes GVL against BC-CML and AML from GVL against CP-CML. This could explain why in the clinic a lower intensity alloimmune response is sufficient to contain mCP-CML whereas such responses are generally insufficient against BC-CML and AML. Our work also suggests that T cells that do not recognize leukemia cells can augment GVL. This hypothesis is consistent with a recent report that early CMV reactivation is associated with a lower risk for AML relapse independent from aGVHD (M.L. Green et al,Blood, 2013). These data provide a strong rationale to develop methods for safely delivering IFN-γ to AML and BC-CML cells post alloSCT. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Yellow Fever Virus Encephalitis: Properties of the Brain-Associated T-Cell Response during Virus Clearance in Normal and Gamma Interferon-Deficient Mice and Requirement for CD4+ Lymphocytes

2001 ◽  
Vol 75 (5) ◽  
pp. 2107-2118 ◽  
Author(s):  
Ting Liu ◽  
Thomas J. Chambers
Keyword(s):  
T Cells ◽  
T Cell ◽  
Yellow Fever ◽  
Gamma Interferon ◽  
T Cell Response ◽  
T Cell Subsets ◽  
Virus Clearance ◽  
Ifn Γ ◽  
The Brain

ABSTRACT Viral encephalitis caused by neuroadapted yellow fever 17D virus (PYF) was studied in parental and gamma interferon (IFN-γ)-deficient (IFN-γ knockout [GKO]) C57BL/6 mice. The T-cell responses which enter the brain during acute fatal encephalitis of nonimmunized mice, as well as nonfatal encephalitis of immunized mice, were characterized for relative proportions of CD4+ and CD8+cells, their proliferative responses, and antigen-specific expression of cytokines during stimulation in vitro. Unimmunized mice accumulated only low levels of T cells within the brain during fatal disease, whereas the brains of immunized mice contained higher levels of both T-cell subsets in response to challenge, with CD8+ cells increased relative to the CD4+ subset. The presence of T cells correlated with the time at which virus was cleared from the central nervous system in both parental and GKO mice. Lymphocytes isolated from the brains of challenged immunized mice failed to proliferate in vitro in response to T-cell mitogens or viral antigens; however, IFN-γ, interleukin 4 (IL-4), and, to a lesser extent, IL-2 were detectable after stimulation. The levels of IFN-γ, but not IL-2 or IL-4, were augmented in response to viral antigen, and this specificity was detectable in the CD4+ compartment. When tested for the ability to survive both immunization and challenge with PYF virus, GKO and CD8 knockout mice did not differ from parental mice (80 to 85% survival), although GKO mice exhibited a defect in virus clearance. In contrast, CD4 knockout and Igh-6 mice were unable to resist challenge. The data implicate antibody in conjunction with CD4+ lymphocytes bearing a Th1 phenotype as the critical factors involved in virus clearance in this model.

scholarly journals Idiotype Immunization Combined With Granulocyte-Macrophage Colony-Stimulating Factor in Myeloma Patients Induced Type I, Major Histocompatibility Complex–Restricted, CD8- and CD4-Specific T-Cell Responses

Blood ◽  
1998 ◽  
Vol 91 (7) ◽  
pp. 2459-2466 ◽  
Author(s):  
Anders Österborg ◽  
Qing Yi ◽  
Lotta Henriksson ◽  
Jan Fagerberg ◽  
Susanne Bergenbrant ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Response ◽  
Type I ◽  
Gm Csf ◽  
Histocompatibility Complex ◽  
Macrophage Colony Stimulating Factor ◽  
Ifn Γ ◽  
Macrophage Colony ◽  
Stimulating Factor

Idiotypic structures expressed on the myeloma Ig protein might be regarded as a tumor-specific antigen. Five patients with IgG myeloma were immunized with the purified serum M-component by repeated intradermal injections together with soluble granulocyte-macrophage colony-stimulating factor (GM-CSF). All patients developed an idiotype (Id)-specific T-cell immunity, defined as blood T cells predominantly secreting interferon-γ (IFN-γ) and interleukin-2 (IL-2) (type I cells). Id-specific DNA synthesis was induced in one patient. Delayed-type hypersensitivity against the Id was not evoked. The specific IFN-γ/IL-2 T-cell response was inhibited (46% to 100%) by a major histocompatibility complex (MHC) class I monoclonal antibody (MoAb) in all five patients. A 5% to 37% inhibition by an MHC class II MoAb was seen in four patients. CD4+ as well as CD8+ T cells enriched by magnetic microbeads contained Id-specific cells. The T cells recognized peptides corresponding to the complementarity-determining regions 1, 2, and 3 of the heavy chain of the Id. There was a transient rise of B cells producing IgM anti-idiotypic antibodies in all patients. The results indicate that immunization of myeloma patients using the autologous M-component and soluble GM-CSF may evoke an Id-specific predominantly MHC class I–restricted type I T-cell response.

scholarly journals Idiotype Immunization Combined With Granulocyte-Macrophage Colony-Stimulating Factor in Myeloma Patients Induced Type I, Major Histocompatibility Complex–Restricted, CD8- and CD4-Specific T-Cell Responses

Blood ◽  
1998 ◽  
Vol 91 (7) ◽  
pp. 2459-2466 ◽  
Author(s):  
Anders Österborg ◽  
Qing Yi ◽  
Lotta Henriksson ◽  
Jan Fagerberg ◽  
Susanne Bergenbrant ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Response ◽  
Type I ◽  
Gm Csf ◽  
Histocompatibility Complex ◽  
Macrophage Colony Stimulating Factor ◽  
Ifn Γ ◽  
Macrophage Colony ◽  
Stimulating Factor

Abstract Idiotypic structures expressed on the myeloma Ig protein might be regarded as a tumor-specific antigen. Five patients with IgG myeloma were immunized with the purified serum M-component by repeated intradermal injections together with soluble granulocyte-macrophage colony-stimulating factor (GM-CSF). All patients developed an idiotype (Id)-specific T-cell immunity, defined as blood T cells predominantly secreting interferon-γ (IFN-γ) and interleukin-2 (IL-2) (type I cells). Id-specific DNA synthesis was induced in one patient. Delayed-type hypersensitivity against the Id was not evoked. The specific IFN-γ/IL-2 T-cell response was inhibited (46% to 100%) by a major histocompatibility complex (MHC) class I monoclonal antibody (MoAb) in all five patients. A 5% to 37% inhibition by an MHC class II MoAb was seen in four patients. CD4+ as well as CD8+ T cells enriched by magnetic microbeads contained Id-specific cells. The T cells recognized peptides corresponding to the complementarity-determining regions 1, 2, and 3 of the heavy chain of the Id. There was a transient rise of B cells producing IgM anti-idiotypic antibodies in all patients. The results indicate that immunization of myeloma patients using the autologous M-component and soluble GM-CSF may evoke an Id-specific predominantly MHC class I–restricted type I T-cell response.

scholarly journals CD4+ T Cells Play a Dominant Role in Protection against New World Leishmaniasis Induced by Vaccination with the P-4 Amastigote Antigen

2005 ◽  
Vol 73 (6) ◽  
pp. 3823-3827 ◽  
Author(s):  
Sujata Kar ◽  
Christine Metz ◽  
Diane McMahon-Pratt
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Response ◽  
Macrophage Migration Inhibitory Factor ◽  
New World ◽  
Dominant Role ◽  
T Cell Response ◽  
Ifn Γ ◽  
Necrosis Factor

ABSTRACT Immunodepletion studies of P-4-vaccinated mice indicate that CD4+ and not CD8+ T cells are critical for protection against Leishmania pifanoi (Leishmania mexicana complex). Although a moderate CD8+ T-cell response is elicited by vaccination, CD4+ T cells are the dominant responding population in vitro and at the cutaneous site of infection. These protective T cells produce gamma interferon (IFN-γ), macrophage migration inhibitory factor (MIF), and tumor necrosis factor/lymphotoxin (TNF/LT), each of which significantly contributed to intracellular parasite destruction in vitro. These results indicate that a singular CD4+ T-cell response (IFN-γ, MIF, and/or LT/TNF) can provide protection against New World cutaneous leishmaniasis.

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