Based on observations that DBA/2 mice develop a highly specific response towards an HLA-Cw3-derived epitope, consisting entirely of CD8+CD62L-Vbeta10+ cells, we have established an in vivo mouse model for screening a variety of immunization approaches. Responder cells were readily detectable in small samples of the peripheral blood using three-color FACS ...

During the course of investigating T cell responses to HSV among volunteers entering trials of investigational genital herpes vaccines, 6 of the 24 immunocompetent subjects with no prior history of oral/labial or genital herpes possessed HSV-specific T cell immunity but, by multiple determinants of even the most sensitive serological assays, ...

Death receptor-mediated activation-induced apoptosis of antigen-specific T cells is a major mechanism of peripheral tolerance induction and immune homeostasis. Failure to undergo activation-induced cell death (AICD) is an important underlying cause of many autoimmune diseases. Thus, enhancing the T cell's own suicide mechanism may provide an efficient therapy for the ...

Immunization with vaccinia virus resulted in long-lasting protection against smallpox and was the approach used to eliminate natural smallpox infections worldwide. Due to the concern about the potential use of smallpox virus as a bioweapon, smallpox vaccination is currently being reintroduced. Severe complications from vaccination were associated with congenital or ...

Innate immunity as a first defense is indispensable for host survival against infectious agents. We examined the roles of natural killer (NK) T cells in defense against Trypanosoma cruzi infection. The T. cruzi parasitemia and survival of CD1d-deficient mice exhibited no differences compared to wild-type littermates. NK T-cell activation induced ...

Discredited a few years ago, active suppression is now commonly considered as a key mechanism avoiding auto-reactivity and development of potentially harmful immune responses, and in some circumstances, as an obstacle to successful vaccination. A large quantity of literature identifies naturally occurring CD4+CD25+ T cells as key suppressor cells involved ...

Memory CD8 T cells can be divided into two subsets, central (T(CM)) and effector (T(EM)), but their lineage relationships and their ability to persist and confer protective immunity are not well understood. Our results show that T(CM) have a greater capacity than T(EM) to persist in vivo and are more ...

There is now convincing evidence that children who develop lower respiratory symptoms during infection with respiratory syncytial virus (RSV) in early life are at increased risk of developing asthma-like symptoms during the school years. What determines this association is not well-understood, but increased likelihood of allergic sensitization plays a minor ...

Genital human papillomavirus (HPV) infection is common and the majority of infected individuals successfully deal with this virus. Clearance of HPV is presumably mediated by T cells but HPV-16-specific T-cell memory was usually detected in patients with progressive disease and not in healthy subjects, suggesting that HPV-immunity comes too late. ...

T lymphocytes play a central role in the generation of a protective immune response in many microbial infections. After immunization, dendritic cells take up microbial antigens and traffic to draining lymph nodes where they present processed antigens to naïve T cells. These naïve T cells are stimulated to proliferate and ...

In addition to its established role in innate immune mechanisms, complement component C3 is also of critical importance in B cell activation and T cell-dependent Ab responses. In this study, we have examined the requirement for C3 in the generation of primary CD8 T cell responses to an acute systemic ...

Initiation and propagation of the immune response is the result of a series of coordinated cellular and biochemical interactions that lead to the activation of multiple cell types. It is now clear that an optimal immune response requires precise and rapid communication between different cell subsets. This phenomenon, referred to ...

4-1BB (CD137) is induced on activated CD4(+) and CD8(+) T cells and delivers a costimulatory signal upon binding the 4-1BB ligand (4-1BBL) expressed on antigen-presenting cells. Induction of 4-1BB is dependent on activation via the T-cell receptor (TCR) and possibly CD28. It was previously demonstrated that both an in vivo ...

Chlamydia trachomatis is one of the major causes of bacterial sexually transmitted disease worldwide. The initial infection of endocervical epithelium in females is asymptomatic and commonly ascends to fallopian tubes when left untreated. Immunity to Chlamydia develops after infection and appears to provide short-term protection. Consequently, a significant rate of ...

Neonates are thought to mount less vigorous adaptive immune responses than adults to antigens and infectious agents. This concept has led to a delay in the administration of many currently available vaccines until late infancy or early childhood. It has recently been shown that vaccines composed of plasmid DNA can ...

An efficent antitumor and antiviral cellular immune response requires optimal interferon-gamma (IFN-gamma) secretion and perforin expression in CD8(+) T cells. The aim of this study was to define whether CD4(+) and CD8(+) T cells from patients with undifferentiated carcinoma of nasopharyngeal type (UCNT), a tumor regularly associated with the Epstein-Barr ...

Ag-presenting dendritic cells present viral Ags to T cells after uptake of apoptotic bodies derived from virus-infected cells in vitro. However, it is unclear whether apoptotic virus-infected cells are capable of generating immunity in vivo. In this study, we show that inoculation of mice with apoptotic HIV-1/murine leukemia virus (MuLV)-infected ...

Recently, childhood asthma has been associated with an alarming rise in prevalence, morbidity, and mortality. Strong epidemiological evidence now links the development of childhood asthma with the persistence of T-helper lymphocyte type 2 (Th2) cytokine immune responses during early infancy. However, the ontogeny of human cytokine immune responses and the ...

Dendritic cells (DCs) are potent APCs for naive CD8(+) T cells and are being investigated as vaccine delivery vehicles. In this study, we examine the CD8(+) T cell response to defined peptides from Listeria monocytogenes (LM), lymphocytic choriomeningitis virus, and murine CMV coated singly and in combination onto mature bone ...

The correlates of protective immunity to disease-inducing viruses in humans remain to be elucidated. We determined the kinetics and characteristics of cytomegalovirus (CMV)-specific CD4(+) and CD8(+) T cells in the course of primary CMV infection in asymptomatic and symptomatic recipients of renal transplants. Specific CD8(+) cytotoxic T lymphocyte (CTL) and ...

In BALB/c mice, sensitization with the attachment protein (G) of respiratory syncytial virus (RSV) leads to CD4(+) T cell-mediated lung eosinophilia during subsequent challenge with RSV. In this study, we originally intended to test whether activation of RSV-specific cytotoxic T cells by peptide-pulsed dendritic cells (DC) after G protein sensitization ...

Modalities for inducing long-lasting immune responses are essential components of vaccine design. Most currently available immunological adjuvants empirically used for this purpose cause some inflammation, limiting clinical acceptability. We show that pentoxifylline (PF), a phosphodiesterase (PDE) inhibitor in common clinical use, enhances long-term persistence of T cell responses, including protective ...

PROBLEM: As shown previously, gp96-Ig peptide complexes secreted by an ovalbumin transfected tumor (EG7) mediate strong, specific tumor immunity through a CD4 T cell independent CD8+ CTL response. In this study, we set out to develop a system to quantitatively determine the CD8 CTL response to gp96-Ig and to evaluate ...

The host immune factors that determine susceptibility to HIV-1 infection are poorly understood. We compared multiple immunologic parameters in three groups of HIV-1-seronegative men: 14 highly exposed (HR10), 7 previously reported possibly to have sustained transient infection (PTI), and a control group of 14 low risk blood bank donors (BB). ...

Bronchiolitis caused by respiratory syncytial virus (RSV) infection is a major cause of hospitalization in children under 1 years of age. The disease characteristically does not induce protective immunity. However, a mononuclear peribronchiolar and perivascular infiltrate during RSV infection is suggestive of an immune-mediated pathogenesis. Macrophages and dendritic cells (DCs) ...

The contribution of T cell responses to immunity against respiratory syncytial virus (RSV) is not fully defined, but this is an important issue for vaccine design. Recent studies demonstrating RSV-induced pulmonary T cell suppression suggest that RSV may have evolved strategies to escape T cell immunity. Here we evaluated potential ...

CD8(+) T cells play an essential role in immunity to Chlamydia pneumoniae (Cpn). However, the target Ags recognized by Cpn-specific CD8(+) T cells have not been identified, and the mechanisms by which this T cell subset contributes to protection remain unknown. In this work we demonstrate that Cpn infection primes ...

Cytomegalovirus (CMV) retinitis is a re-activation infection associated with severely impaired T cell-mediated immunity. We describe a patient with long-standing Crohn's disease and thymoma who developed severe CMV retinitis. While thymoma can be associated with impaired humoral immunity and a quantitative CD4+ T helper cell deficiency, these were not evident ...

The efficacy of intramammary (Ima) immunization with a live attenuated (la) Staphylococcus aureus mutant to protect the mouse mammary gland from infection has previously been established. The present study was aimed at evaluating whether Ima immunization with la-S. aureus can induce cell-mediated immune responses to the pathogen within the mammary ...

We compared the effects of live or inactivated bovine respiratory syncytial virus (BRSV) on cytokine production by bovine monocyte-derived dendritic cells (MoDC). We also investigated the response of resting memory CD4(+) T cells to MoDC exposed to both viral preparations. Although BRSV did not appear to replicate in MoDC or ...

Despite the seriously undernourished state of patients with anorexia nervosa (AN) and bulimia nervosa (BN), controversial findings have been published regarding some aspects of the immune system that are otherwise impaired in more typical types of malnutrition, such as protein-energy malnutrition. In general, adaptation processes seem to occur enabling immune ...

The identification of T cell epitopes that elicit a weak T cell response is technically challenging due to the relatively low resolution of many available screening assays. Peptide immunization can confirm the immunogenicity of a given peptide, however, this also often induces a low frequency response in lymphoid organs. In ...

Since the discovery of 4-1BB 15 years ago, the receptor and its ligand (4-1BBL) have remained enigmatic molecules because of their highly regulated pattern of expression. Classically, 4-1BB is known to function as a costimulator for T cells and as a potent survival factor for CD8+ T cells. Recent studies ...

Mice infected with the murine coronavirus, mouse hepatitis virus, strain JHM (MHV) develop an immune-mediated demyelinating encephalomyelitis. Adoptive transfer of MHV-immune splenocytes depleted of either CD4 or CD8 T cells to infected mice deficient in recombination activation gene 1 resulted in demyelination. We showed previously that the process of CD8 ...

Actinobacillus pleuropneumoniae bacterins do not induce protection in pigs while infection with low doses of the CM5 strain of A. pleuropneumoniae given by aerosol induces complete protection. To evaluate possible correlates of protection in blood lymphocyte subset phenotypes, pigs were treated with a commercial bacterin given intramuscularly, low dose (10(5)cfu/ml) ...

Infection with pathogens often leads to loss of body weight, but the cause of weight loss during infection is poorly understood. We used the infection of mice with lymphocytic choriomeningitis virus (LCMV) as a model to study how pathogens induce weight loss. If LCMV is introduced into the CNS of ...

The oligonucleotides coding for three epitopes (HA91-108, NP55-69, and NP 147-158) of influenza virus, stimulating B-cells, T-helper cells and cytotoxic T lymphocytes (CTLs), respectively, were previously employed for expressing each epitope in flagella that induced specific humoral and cellular immune responses. We have constructed new plasmids expressing all three epitopes ...

A growth compromised herpes simplex virus type 2 (HSV-2) mutant which is deleted in the PK domain of the large subunit of ribonucleotide reductase (ICP10DeltaPK) protects from HSV-2 challenge in the mouse and guinea pig cutaneous and vaginal models and reduces the incidence and frequency of recurrent disease (Vaccine (17) ...

During a viral response, Ag-specific effector T cells show dramatically increased binding by the mAb 1B11 and the lectin peanut agglutinin (PNA). We investigated the contribution of CD43 expression to 1B11 and PNA binding as well as its role in generation and maintenance of a CD8 T cell response. Analysis ...

Interferon (IFN)-gamma-producing CD8+ T cells are important for the successful resolution of the obligate intracellular parasite Toxoplasma gondii by preventing the reactivation or controlling a repeat infection. Previous reports from our laboratory have shown that exogenous interleukin (IL)-15 treatment augments the CD8+ T cell response against the parasite. However, the ...

Apoptosis is critical to the progression of human immunodeficiency virus-1 (HIV-1) infection. It appears reasonable that antiretroviral therapies may not achieve a full control of the infection in the absence of an impact on apoptosis. We assigned 20 asymptomatic HIV-infected subjects with advanced immunodeficiency to receive either zidovudine (AZT), and ...

Adhesins are considered the most important virulence factors during early phases Staphylococcus aureus infection. Antibodies induced by vaccination toward an adhesin should reduce the adherence of the pathogen and augment its phagocytosis. The present report describes the immune response of mice to a DNA vaccine directed against one of these ...

To determine whether attenuated simian immunodeficiency virus (SIV) vaccines confer protection against superinfection via secondary cellular immune responses, we searched for markers of immune activation following rechallenge. Productive infection with either attenuated SIVmacC8 or wild-type SIVmacJ5 resulted in a transient increase in T-lymphocyte CD25 and Mafa-DR expression. A pronounced increase ...

We previously demonstrated that immunization of mice with plasmid DNAs (pDNAs) expressing the murine cytomegalovirus (MCMV) genes IE1-pp89 and M84 provided synergistic protection against sublethal viral challenge, while immunization with plasmids expressing putative virion proteins provided no or inconsistent protection. In this report, we sought to augment protection by increasing ...

The cellular immune response to respiratory syncytial virus (RSV) infection was examined in infants aged 1-21 months who were hospitalized because of RSV infection or non-RSV-related illness. RSV- or control-stimulated peripheral blood mononuclear cells were examined to determine RSV-specific intracellular T helper-1 (Th1) and T helper- 2 (Th2) cytokine expression, ...

RSV is an important cause of bronchiolitis in infants. Immunopathology may play a role in RSV-induced bronchiolitis and severe RSV-induced disease has been associated with a Th2 type immune response. The aim of the study was to identify cytokine pathways that are crucial in influencing RSV-induced disease. For that purpose ...

We previously showed that intradermal immunization with plasmids expressing the murine cytomegalovirus (MCMV) protein IE1-pp89 or M84 protects against viral challenge and that coimmunization has a synergistic protective effect (C. S. Morello, L. D. Cranmer, and D. H. Spector, J. Virol. 74:3696-3708, 2000). Using an intracellular gamma interferon cytokine staining ...

Mice infected with the murine coronavirus, mouse hepatitis virus, strain JHM (MHV) develop an immune-mediated demyelinating encephalomyelitis. We showed previously that adoptive transfer of MHV-immune splenocytes depleted of either CD4 or CD8 T cells to infected RAG1(-/-) recipients (mice deficient in recombination activation gene 1) resulted in demyelination. Herein we ...

In vitro cytokine production in response to respiratory syncytial virus (RSV) and influenza infections was investigated in 11 "young" (mean age, 31 years) and "older" (mean age, 75 years) healthy volunteers by use of interferon (IFN)-gamma ELISPOT and ELISA analysis of cytokines in culture supernatants. Autologous dendritic cells (DCs), derived ...

Chlamydia trachomatis is the most common cause of bacterial sexually transmitted disease in the United States, as well as the leading cause of preventable blindness worldwide. Immunity to C. trachomatis requires a variety of cell types, each employing an array of effector functions. Recent work has demonstrated that both CD4+ ...