Delayed Hypersensitivity to Toxoplasma and Unrelated Antigens in Toxoplasma -Infected Mice: Induction and Elicitation of Delayed-Type Hypersensitivity by Antigen-Pulsed Macrophages

1980 ◽  
Vol 28 (2) ◽  
pp. 524-531 ◽  
Author(s):  
Emanuela Handman ◽  
Patrice M. Chester ◽  
Jack S. Remington
Keyword(s):  
T Cells ◽  
Antibody Response ◽  
Chronic Infection ◽  
Chronic Phase ◽  
Keyhole Limpet Hemocyanin ◽  
Delayed Type Hypersensitivity ◽  
Intracellular Parasites ◽  
Infected Cells ◽  
Uptake Method ◽  
Formalin Fixed

Delayed-type hypersensitivity (DTH) to Toxoplasma and unrelated antigens in Toxoplasma -infected BALB/c mice was investigated by the radioisotopic uptake method of Vadas et al. (Int. Arch. Allergy Appl. Immunol. 49: 670-692, 1975). DTH became positive on day 30 of infection and remained positive during chronic infection. The expression of DTH in mice infected with the relatively avirulent C37 strain of the parasite paralleled the Toxoplasma antibody response as detected by the Sabin-Feldman dye test. Mice sensitized with Toxoplasma , keyhole limpet hemocyanin, or sheep erythrocytes during the acute or chronic phase of Toxoplasma infection showed a DTH reaction similar to that of uninfected sensitized controls. No parasite antigens could be detected by immunofluorescence techniques on the surface of Toxoplasma -infected cells. When killed organisms were added to the cell cultures, specks of fluorescence appeared on cells containing intracellular parasites as well as on cells without intracellular organisms. That the antigens may be present in or on macrophages in a form readily recognizable by T cells is suggested by experiments in which we demonstrated that injection of uninfected normal macrophages pulsed with Toxoplasma -soluble antigens into the ears of chronically infected mice elicited a DTH reaction comparable to that observed when 10 6 Formalin-fixed tachyzoites were used as the test antigen. When macrophages pulsed with Toxoplasma antigen were used in attempts to induce DTH in naive uninfected mice, the intensity of the reaction was similar to that observed in infected mice.

scholarly journals Notwithstanding Circumstantial Alibis, Cytotoxic T Cells Can Be Major Killers of HIV-1-Infected Cells

2016 ◽  
Vol 90 (16) ◽  
pp. 7066-7083 ◽  
Author(s):  
Saikrishna Gadhamsetty ◽  
Tim Coorens ◽  
Rob J. de Boer
Keyword(s):  
T Cells ◽  
Viral Replication ◽  
Cytotoxic T Cells ◽  
Chronic Phase ◽  
Replication Rate ◽  
Immunodeficiency Virus ◽  
Infected Cells ◽  
Eclipse Phase ◽  
Hiv 1

ABSTRACTSeveral experiments suggest that in the chronic phase of human immunodeficiency virus type 1 (HIV-1) infection, CD8+cytotoxic T lymphocytes (CTL) contribute very little to the death of productively infected cells. First, the expected life span of productively infected cells is fairly long, i.e., about 1 day. Second, this life span is hardly affected by the depletion of CD8+T cells. Third, the rate at which mutants escaping a CTL response take over the viral population tends to be slow. Our main result is that all these observations are perfectly compatible with killing rates that are much faster than one per day once we invoke the fact that infected cells proceed through an eclipse phase of about 1 day before they start producing virus. Assuming that the major protective effect of CTL is cytolytic, we demonstrate that mathematical models with an eclipse phase account for the data when the killing is fast and when it varies over the life cycle of infected cells. Considering the steady state corresponding to the chronic phase of the infection, we find that the rate of immune escape and the rate at which the viral load increases following CD8+T cell depletion should reflect the viral replication rate, ρ. A meta-analysis of previous data shows that viral replication rates during chronic infection vary between 0.5 ≤ ρ ≤ 1 day−1. Balancing such fast viral replication requires killing rates that are several times larger than ρ, implying that most productively infected cells would die by cytolytic effects.IMPORTANCEMost current data suggest that cytotoxic T cells (CTL) mediate their control of human immunodeficiency virus type 1 (HIV-1) infection by nonlytic mechanisms; i.e., the data suggest that CTL hardly kill. This interpretation of these data has been based upon the general mathematical model for HIV infection. Because this model ignores the eclipse phase between the infection of a target cell and the start of viral production by that cell, we reanalyze the same data sets with novel models that do account for the eclipse phase. We find that the data are perfectly consistent with lytic control by CTL and predict that most productively infected cells are killed by CTL. Because the killing rate should balance the viral replication rate, we estimate both parameters from a large set of published experiments in which CD8+T cells were depleted in simian immunodeficiency virus (SIV)-infected monkeys. This confirms that the killing rate can be much faster than is currently appreciated.

scholarly journals Acceptor-suppressor T cell hybridoma with a receptor recognizing antigen-specific suppressor factor.

1983 ◽  
Vol 158 (6) ◽  
pp. 1912-1923 ◽  
Author(s):  
I Takei ◽  
T Sumida ◽  
M Taniguchi
Keyword(s):  
T Cells ◽  
T Cell ◽  
Antibody Response ◽  
Keyhole Limpet Hemocyanin ◽  
Acceptor Site ◽  
Suppressor Factor ◽  
T Cell Factor ◽  
Suppressor T Cell ◽  
Antigen System ◽  
Petri Dishes

An acceptor hybridoma with a receptor that recognizes the keyhole limpet hemocyanin (KLH)-specific suppressor T cell factor (KLH-TsF) was established after the fusion of C57BL/6 splenic T cells enriched with KLH-coated petri dishes. The cloned hybridoma (34S-281) could be specifically activated by stimulation with the conventional KLH-TsF or monoclonal KLH-TsF from three different hybridomas in the absence of the relevant antigen (KLH) and it started to produce another factor that suppresses the antibody response against DNP-KLH in a KLH-specific fashion. The KLH specificity of the TsF was required for activation. The new factor was found not to bind the KLH but to be absorbed with the KLH-TsF-producing hybridoma. It is thus strongly suggested that the acceptor site has a complementary structure (antiidiotype) for the KLH-TsF. Moreover, the idiotypic determinant on KLH-TsF was found to have a structure similar to that on some of the anti-KLH antibodies, since the acceptor hybridoma was specifically killed by the conventional anti-KLH antibodies and complement. Drawing on the above results, the idiotype-antiidiotype network in the conventional antigen system is discussed.

scholarly journals During Trypanosoma cruzi Infection CD1d-Restricted NK T Cells Limit Parasitemia and Augment the Antibody Response to a Glycophosphoinositol-Modified Surface Protein

2002 ◽  
Vol 70 (1) ◽  
pp. 36-48 ◽  
Author(s):  
Malcolm S. Duthie ◽  
Monika Wleklinski-Lee ◽  
Sherilyn Smith ◽  
Toshinori Nakayama ◽  
Masaru Taniguchi ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Antibody Response ◽  
Inflammatory Responses ◽  
Chronic Phase ◽  
Surface Protein ◽  
Nk T Cells ◽  
Modified Surface ◽  
Nk T Cell ◽  
Deficient Mice

ABSTRACT Trypanosoma cruzi is a protozoan parasite that chronically infects many mammalian species and in humans causes Chagas’ disease, a chronic inflammatory disease. The parasite expresses glycophosphoinositol (GPI), which potently stimulates interleukin 12 (IL-12) production. During T. cruzi infection IL-12, and possibly GPI, might stimulate NK T cells to affect the protective and chronic inflammatory responses. Here we report that during T. cruzi infection CD1d-restricted NK T cells are stimulated as NK T-cell-deficient mice have greater parasitemia. Furthermore, during T. cruzi infection the percentages of NK T cells in the liver and spleen become decreased for prolonged periods of time, and in vitro stimulation of NK T cells derived from livers of chronically infected mice, compared to uninfected mice, results in increased gamma interferon and IL-4 secretion. Moreover, in NK T-cell-deficient mice the chronic-phase antibody response to a GPI-modified surface protein is decreased. These results indicate that, during the acute infection, NK T cells limit parasitemia and that, during the chronic phase, NK T cells augment the antibody response. Thus, during T. cruzi infection the quality of an individual’s NK T-cell response can affect the level of parasitemia and parasite tissue burden, the intensity of the chronic inflammatory responses, and possibly the outcome of Chagas’ disease.

scholarly journals Anti-idiotype induced regulation of helper cell function for the response to phosphorylcholine in adult BALB/c mice.

1978 ◽  
Vol 148 (5) ◽  
pp. 1216-1227 ◽  
Author(s):  
K Bottomly ◽  
B J Mathieson ◽  
D E Mosier
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Antibody Response ◽  
Gamma Globulin ◽  
Cell Function ◽  
Keyhole Limpet Hemocyanin ◽  
Secondary Antibody ◽  
Suppressor T Cells ◽  
Helper Activity

An adoptive secondary antibody response to phosphorylcholine (PC) can be generated by the transfer of keyhole limpet hemocyanin (KLH)-primed T cells, PC-bovine gamma globulin-primed B cells, and PC-KLH into irradiated syngeneic BALB/c mice. If the KLH-primed T-cell donors were pretreated with anti-idiotype antibodies directed against the BALB/c PC-binding myeloma TEPC 15, their T cells were unable to collaborate effectively with PC-primed B cells; moreover, they could suppress the helper activity of T cells from normal mice for the PC-KLH response. The Ly phenotype of these T cells was found to be Ly 1-, 2+. The specificity of the suppressor T-cell population induced by anti-T15 treatment appears to be both for idiotype (hapten) and carrier, since the suppressor T cells fail to interfere with the antibody response to PC on a heterologous carrier, nor do they suppress the response to trinitrophenol-KLH.

scholarly journals RESTORATION OF CELL-MEDIATED IMMUNITY TO ANIMALS BLOCKED BY A HUMORAL RESPONSE

1974 ◽  
Vol 140 (3) ◽  
pp. 865-870 ◽  
Author(s):  
George B. MacKaness ◽  
Philippe H. Lagrange
Keyword(s):  
T Cells ◽  
Antibody Response ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Humoral Response ◽  
Delayed Type Hypersensitivity ◽  
Cell Mediated Immunity ◽  
Continuous Exposure ◽  
Long Period ◽  
Blocking Factors

The T cells which mediate delayed-type hypersensitivity (DTH) to sheep red blood cells (SRBC) are blocked by a normal humoral response and cannot be made to function by further immunization. They can be rescued to some extent by treatment with immunopotentiating agents such as cyclophosphamide (CY) which suppresses the antibody response selectively, or by BCG which interferes with the action of serum blocking factors. These two agents together can restore cell-mediated immunity completely, but a further antigenic stimulus is needed to reestablish DTH in mice blocked by a long period of continuous exposure to SRBC.

scholarly journals Loss of the signaling adaptor TRAF1 causes CD8+ T cell dysregulation during human and murine chronic infection

2011 ◽  
Vol 209 (1) ◽  
pp. 77-91 ◽  
Author(s):  
Chao Wang ◽  
Ann J. McPherson ◽  
R. Brad Jones ◽  
Kim S. Kawamura ◽  
Gloria H.Y. Lin ◽  
...  
Keyword(s):  
T Cells ◽  
Viral Load ◽  
T Cell ◽  
Cd8 T Cells ◽  
Chronic Infection ◽  
Chronic Phase ◽  
Cd8 T Cell ◽  
Dependent Manner ◽  
Viral Control ◽  
Potential Biomarker

The signaling adaptor TNFR-associated factor 1 (TRAF1) is specifically lost from virus-specific CD8 T cells during the chronic phase of infection with HIV in humans or lymphocytic choriomeningitis virus (LCMV) clone 13 in mice. In contrast, TRAF1 is maintained at higher levels in virus-specific T cells of HIV controllers or after acute LCMV infection. TRAF1 expression negatively correlates with programmed death 1 expression and HIV load and knockdown of TRAF1 in CD8 T cells from viral controllers results in decreased HIV suppression ex vivo. Consistent with the desensitization of the TRAF1-binding co-stimulatory receptor 4-1BB, 4-1BBL–deficient mice have defects in viral control early, but not late, in chronic infection. TGFβ induces the posttranslational loss of TRAF1, whereas IL-7 restores TRAF1 levels. A combination treatment with IL-7 and agonist anti–4-1BB antibody at 3 wk after LCMV clone 13 infection expands T cells and reduces viral load in a TRAF1-dependent manner. Moreover, transfer of TRAF1+ but not TRAF1− memory T cells at the chronic stage of infection reduces viral load. These findings identify TRAF1 as a potential biomarker of HIV-specific CD8 T cell fitness during the chronic phase of disease and a target for therapy.

A Novel Strategy for Combining Immunotherapy with High Dose Chemotherapy and Auto-Transplantation in High Risk Multiple Myeloma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2920-2920
Author(s):  
Susann Szmania ◽  
Michele Cottler-Fox ◽  
Nancy Rosen ◽  
Sanjaya Viswamitra ◽  
Amberly Moreno ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
T Cells ◽  
High Risk ◽  
Complete Remission ◽  
Antibody Response ◽  
Autologous Transplantation ◽  
High Dose Chemotherapy ◽  
Delayed Type Hypersensitivity ◽  
High Dose ◽  
Novel Strategy

Abstract Although high dose chemotherapy and autologous transplantation (AT) can induce complete remission in approximately 50% of multiple myeloma (MM) patients, the majority eventually relapse. We hypothesize that a combination of AT and vaccination may sustain remissions by inducing specific cytotoxic T cells against chemotherapy resistant plasma cells. Vaccinations are typically given after AT when the immune system is very defective. We tested the novel strategy of priming anti-myeloma T-cells before AT and protecting the primed T-cells from high-dose chemotherapy by apheresis and cryopreservation of the primed cells. After high-dose chemotherapy induced cytoreduction, the primed T-cells were returned early after AT and preferentially expanded by a series of booster vaccinations (figure 1). The vaccines are monocyte derived-dendritic cells (DC) loaded with myeloma lysate (ML) and tracer antigen keyhole limpet hemocyanin (KLH), matured with trimeric CD40-ligand, administered intranodally, and followed by 5 days of low dose subcutaneous IL-2. Four patients with poor prognosis MM (characterized by abnormal metaphase cytogenetics) have been vaccinated and three are evaluable (the 4th patient is 60 days post AT2 and only 14 days post vaccine 8). ML specific immune responses were detected by delayed type hypersensitivity reactions and proliferation in 2/3 and by ELISPOT in 3/3 patients. Strong responses to KLH were observed in 3/3 patients. The pattern of response is a dramatic and rapid increase in ML specific T cell proliferation (figure 2) and IFN-g secretion after LP2 infusion plus booster vaccinations post AT, suggesting that the primed T-cells had been protected by collection and storage during AT. A high pre-existing ML specific antibody response was observed in 2/3 patients and a low antibody response pre-vaccination was clearly boosted in a third patient. The patient receiving the lowest DC dose (50 versus 115 and 139 x106) had a response to ML only detected by IFNg secretion assays, but is in near complete remission, 719 days post AT2, while disease progression was observed in the other two patients 496 and 626 days after AT. Our immune monitoring data suggest that the problem of applying vaccination in heavily treated patients may be overcome by early vaccination, collection and subsequent reinfusion of primed cells followed by repeated booster vaccination. Optimization of the vaccine regimen by increasing the frequency of vaccination or the use of highly immunogenic, well characterized tumor-associated antigens may further improve efficacy. We have an ongoing trial for high risk MM patients utilizing NY-ESO-1 and MAGE-A3 peptide vaccines based on a similar strategy to preserve immune competence.

scholarly journals SELECTIVE ROLES OF THYMUS-DERIVED LYMPHOCYTES IN THE ANTIBODY RESPONSE

1974 ◽  
Vol 140 (1) ◽  
pp. 253-266 ◽  
Author(s):  
Toshitada Takemori ◽  
Tomio Tada
Keyword(s):  
T Cells ◽  
B Cells ◽  
Antibody Response ◽  
Keyhole Limpet Hemocyanin ◽  
High Avidity ◽  
Spleen Cells ◽  
Suppressor T Cells ◽  
High Affinity ◽  
Specific Suppressor T Cells ◽  
Selection Of

Passive transfer of thymocytes and spleen cells from donors primed with keyhole limpet hemocyanin (KLH) caused significant decrease in the average avidity of anti-DNP antibodies produced by direct and indirect PFC in the recipients in both primary and adoptive secondary antibody responses against DNP-KLH. The analysis of the avidity distribution of antibodies produced by plaque-forming cells (PFC) indicated that the observed decrease in the average avidity is primarily due to the selective loss of high avidity subpopulation of PFC leaving low avidity subpopulation relatively unaffected. The degree of suppression in antibody avidity did not correlate with the reduction in the number of PFC, and thus causing the "shift" of avidity distribution of PFC to the low avidity end. These results indicate that the "maturation" of antibody in the T-cell-dependent antibody response is influenced by the carrier-specific suppressor T cells with respect to the emergence and selection of B cells having high affinity receptors for hapten. It is suggested that B cells binding antigen with high affinity receptors would be more easily affected than those with low affinity receptors by specific suppressor T cells which are capable of reacting the carrier portion of the same antigen.

scholarly journals Absence of SIV-specific CD8+ T cells in germinal centers may set the stage for persistent infection

2018 ◽  
Author(s):  
Shengbin Li ◽  
Joy M. Folkvord ◽  
Katalin J Kovacs ◽  
Reece K. Wagstaff ◽  
Gwantwa Mwakalundwa ◽  
...  
Keyword(s):  
T Cells ◽  
B Cell ◽  
Cd8 T Cells ◽  
Persistent Infection ◽  
Chronic Infection ◽  
Chronic Phase ◽  
Germinal Centers ◽  
Early Infection ◽  
Viral Rna ◽  
Lymphoid Follicles

AbstractCD8+ T cells play an important role in controlling of HIV and SIV infections. However, these cells are largely excluded from B cell follicles where HIV and SIV producing cells concentrate during chronic infection. It is not known, however, if antigen-specific CD8+ T cells are excluded gradually as pathogenesis progresses from early to chronic phase, or this phenomenon occurs from the beginning infection. In this study we determined that SIV-specific CD8+ T cells were largely excluded from follicles during early infection, we also found that within follicles, they were entirely absent in 60% of the germinal centers (GCs) examined. Furthermore, levels of SIV-specific CD8+ T cells in follicular but not extrafollicular areas significantly correlated inversely with levels of viral RNA+ cells. In addition, subsets of follicular SIV-specific CD8+ T cells were activated and proliferating and expressed the cytolytic protein perforin. These studies suggest that a paucity of SIV-specific CD8+ T cells in follicles and complete absence within GCs during early infection may set the stage for the establishment of persistent chronic infection.Author SummaryA paucity of SIV-specific CD8+ T cells in lymphoid follicles and complete absence within most follicular germinal centers during early infection may set the stage for the establishment of persistent chronic infection.

scholarly journals Immunomonitoring Tumor-Specific T Cells in Delayed-Type Hypersensitivity Skin Biopsies After Dendritic Cell Vaccination Correlates With Clinical Outcome

2005 ◽  
Vol 23 (24) ◽  
pp. 5779-5787 ◽  
Author(s):  
I. Jolanda M. de Vries ◽  
Monique R. Bernsen ◽  
W. Joost Lesterhuis ◽  
Nicole M. Scharenborg ◽  
Simon P. Strijk ◽  
...  
Keyword(s):  
T Cells ◽  
Clinical Outcome ◽  
Stage Iv ◽  
Keyhole Limpet Hemocyanin ◽  
Delayed Type Hypersensitivity ◽  
Dendritic Cell Vaccination ◽  
Dc Vaccine ◽  
Novel Approach ◽  
Hypersensitivity Skin ◽  
Melanoma Patients

Purpose Tumor-specific immunomonitoring is essential to evaluate the efficacy of vaccination against cancer. In this study, we investigated the predictive value of the presence or absence of antigen-specific T cells in biopsies from delayed-type hypersensitivity (DTH) sites. Patients and Methods In our ongoing clinical trials, HLA-A2.1+ melanoma patients were vaccinated with mature dendritic cells (DC) pulsed with melanoma-associated peptides (gp100 and tyrosinase) and keyhole limpet hemocyanin. Results After intradermal administration of a DTH challenge with gp100- and tyrosinase peptide-loaded DC, essentially all patients showed a positive induration. In clinically responding patients, T cells specific for the antigen preferentially accumulated in the DTH site, as visualized by in situ tetramer staining. Furthermore, significant numbers of functional gp100 and tyrosinase tetramer-positive T cells could be isolated from these DTH biopsies, in accordance with the applied antigen in the DTH challenge. We observed a direct correlation between the presence of DC vaccine-related T cells in the DTH biopsies of stage IV melanoma patients and a positive clinical outcome (P = .0012). Conclusion These findings demonstrate the potency of this novel approach in the monitoring of vaccination studies in cancer patients.

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