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Immunological comparison of HIV-1-, HIV-2- and dually-reactive women delivering in Abidjan, Côte d'Ivoire.

OBJECTIVES: To compare the basic immunological changes induced by HIV-1 and HIV-2 infection and to assess the immune status of subjects serologically reactive to both HIV-1 and HIV-2 (dually-reactive). DESIGN: Immune parameters were studied cross-sectionally in women delivering in Abidjan, Côte d'Ivoire, West Africa, where HIV-1 and HIV-2 are endemic. In this area, a significant number of sera from infected individuals are reactive to both HIV-1 and HIV-2. SUBJECTS AND METHODS: Two hundred and twenty-eight women delivering in a major maternity clinic were screened for HIV-1 and HIV-2 using an enzyme-linked immunosorbent assay. Seropositivity was confirmed by Western blot. The immune parameters studied were CD4+ and CD8+ lymphocyte subsets, immunoglobulin (Ig) serum levels, neopterin and beta 2-microglobulin (beta 2M) serum levels. RESULTS: Similar but less pronounced immune changes were present in HIV-2-reactive subjects compared with HIV-1- and dually-reactive subjects. The observed differences between the HIV-seropositive groups could not be explained by differences in age or disease stage but paralleled differences in the frequency of persistent generalized lymphadenopathy (PGL). The intermediate immune profile of HIV-2-reactives (between seronegatives and HIV-1- and dually-reactives) was most clearly reflected by the number of CD8+ lymphocytes, the CD4:CD8 ratio and the IgG serum level. Median neopterin and beta 2M levels, though significantly increased in all HIV-seropositive groups, did not differ significantly between HIV-2-, HIV-1- and dually-reactives. CONCLUSIONS: HIV-2 infection is associated with typical HIV-related immunological changes. Immunologically, dually-reactives resemble HIV-1-reactives more closely than HIV-2-reactive subjects.

Adult↗

Genetic susceptibility to ozone-induced lung inflammation in animal models of asthma.

PURPOSE OF REVIEW: Epidemiological associations between ozone exposure and allergic responsiveness are well-documented and have been corroborated in animal studies. The complex interaction between ozone and allergen has genetic and environmental components that affect atopic individuals and may increase the incidence of allergy in susceptible individuals. This review describes the advances that have been made in understanding mechanisms of genetic susceptibility to ozone-induced inflammation, and the interaction between ozone and allergen exposure in mice and a non-human primate model. RECENT FINDINGS: Antioxidant and innate immune defense genes contribute to ozone-induced inflammation and hyperpermeability in mice and humans. Ozone exposure during the allergic challenge phase induces greater enhancement of allergic responsiveness than the sensitization stage. Ovalbumin-pulsed dendritic cells injected into naïve mice successfully sensitize the mouse to ovalbumin in the absence of adjuvant. Debate continues over the role of T helper 1-T helper 2 immune profile development in mediating the ozone-allergen interaction, and the potential confounding influence of the predominant T helper 2 system most commonly used to study these responses. SUMMARY: The role of genetic background in susceptibility to ozone-induced lung inflammation has been confirmed, and promising candidate genes have been identified. Descriptive studies confirm that ozone exacerbates allergic responsiveness. Ozone administered during the challenge phase of ovalbumin allergen exposure induces greater responsiveness than during the sensitization phase. Allergen-induced responses enhanced by concurrent ozone exposure warrant further mechanistic research, particularly regarding the influence of susceptibility genes.

Allergens↗

Mindfulness-based stress reduction in relation to quality of life, mood, symptoms of stress, and immune parameters in breast and prostate cancer outpatients.

OBJECTIVES: This study investigated the relationships between a mindfulness-based stress reduction meditation program for early stage breast and prostate cancer patients and quality of life, mood states, stress symptoms, lymphocyte counts, and cytokine production. METHODS: Forty-nine patients with breast cancer and 10 with prostate cancer participated in an 8-week MBSR program that incorporated relaxation, meditation, gentle yoga, and daily home practice. Demographic and health behavior variables, quality of life (EORTC QLQ C-30), mood (POMS), stress (SOSI), and counts of NK, NKT, B, T total, T helper, and T cytotoxic cells, as well as NK and T cell production of TNF, IFN-gamma, IL-4, and IL-10 were assessed pre- and postintervention. RESULTS: Fifty-nine and 42 patients were assessed pre- and postintervention, respectively. Significant improvements were seen in overall quality of life, symptoms of stress, and sleep quality. Although there were no significant changes in the overall number of lymphocytes or cell subsets, T cell production of IL-4 increased and IFN-gamma decreased, whereas NK cell production of IL-10 decreased. These results are consistent with a shift in immune profile from one associated with depressive symptoms to a more normal profile. CONCLUSIONS: MBSR participation was associated with enhanced quality of life and decreased stress symptoms in breast and prostate cancer patients. This study is also the first to show changes in cancer-related cytokine production associated with program participation.

Adenocarcinoma↗

Presence of lysogenic phage in the outbreak strains of Vibrio cholerae O139.

Four outbreak strains of Vibrio cholerae O139 from endemic areas of India and Bangladesh were found to carry lysogenic phage(s). All of these phage(s) produced turbid plaques characteristic of lysogeny on V. cholerae MAK 757 (El Tor, Ogawa) cells as well as on their VcA-1 lysogens but were unable to infect V. cholerae 154 (classical) cells, the universal host for all classical phages. Colonies in the turbid plaques were O139 lysogens and these developed an auxotrophic requirement, mainly for purines suggesting the integration of the prophage into the host chromosome. The immunity profile of the O139 phage(s) was similar to that of phage alpha but differed in the sensitivity of the phage lysogen of V. cholerae MAK 757 to subsequent infection by phage beta.

Bacteriophages↗

Fusion PCR generated Japanese encephalitis virus/dengue 4 virus chimera exhibits lack of neuroinvasiveness, attenuated neurovirulence, and a dual-flavi immune response in mice.

The first flavivirus chimera encoding dengue 4 virus (D4) PrM and E structural proteins in a Japanese encephalitis virus (JEV) backbone was successfully generated using the long-PCR based cDNA-fragment stitching (LPCRcFS) technique, demonstrating the technique's applicability for rapid preparation of flavivirus chimeras. The JEV/D4 chimera multiplied at levels equal to JEV and D4 in the mosquito cell line C6/36, while in a mouse neuronal cell line (N2a) JEV replicated efficiently, but JEV/D4 and D4 did not. In mouse challenge experiments, JEV/D4 showed a lack of neuroinvasiveness similar to D4 when inoculated intraperitoneally, but demonstrated attenuated neurovirulence (LD50=3.17 x 10(4) f.f.u.) when inoculated intracranially. It was also noted that mice receiving intraperitoneal challenge with JEV/D4 possessed D4-specific neutralization antibody and in addition clearly showed resistance to JEV intraperitoneal challenge (at 100 x LD50). This suggests that immunity to anti-JEV non-structural protein(s) offers protection against JEV infection in vivo. Dengue secondary infection was also simulated by challenging mice pre-immunized with dengue 2 virus, with D4 or JEV/D4. Mice showed higher secondary antibody response to challenge with JEV/D4 than to D4, at 210,000 and 37,000 averaged ELISA units, respectively. Taken together, aside from demonstrating the LPCRcFS technique, it could be concluded that the PrM and E proteins are the major determinant of neuroinvasiveness for JEV. It is also expected that the JEV/D4 chimera with its pathogenicity in mice and atypical immune profile, could have applications in dengue prophylactic research, in vivo efficacy assessment of dengue vaccines and development of animal research on models of dengue secondary infection.

Animals↗

The immunobiology of Th1 polarization in high-pathology schistosomiasis.

Schistosomiasis is a serious global helminthic disease, in which the main immunopathology consists of a granulomatous and fibrosing reaction against tissue-trapped parasite eggs. The severity of this inflammatory process, the product of a CD4(+) T-cell-mediated immune response against parasite egg antigens, is, however, markedly uneven, both in human patients and among mouse strains in an experimental model. Severe schistosomiasis is associated with persistently elevated pro-inflammatory T-helper-1 (Th1)-type cytokines, whereas milder pathology is present when Th2 cytokines dominate. This scenario is supported by the pronounced pathology resulting from the obliteration of pathways that facilitate Th2 differentiation and by the development of more intense lesions in mouse strains that fail to downregulate the Th1 response. Genetically prone high-pathology mice have a higher proportion of CD4(+) T cells in lymph nodes and granulomas, in which the Th1 phenotype is driven by interleukin-12; they also develop a dominant repertoire against peptide 234-246 of the major Sm-p40 egg antigen, utilizing a strikingly restricted T-cell receptor structure that involves Valpha11.3beta8. In turn, low-pathology mice exhibit enhanced CD4(+) T-cell apoptosis, which contributes to limit pathology. The definition of distinctive immune profiles associated with polar forms of schistosomiasis opens opportunities for targeted immuno-intervention in individuals suffering from or at risk of severe disease.

Animals↗

Human leucocyte antigen determinants of susceptibility to Barrett's oesophagus in Asians--a preliminary study.

BACKGROUND: Characteristic immune profiles have been demonstrated in gastro-oesophageal reflux disease. However, the genetic basis of gastro-oesophageal reflux disease remains unclear. AIM: To investigate whether certain human leucocyte antigen genes are associated with Barrett's oesophagus. METHODS: Asian patients of Malay, Chinese and Indian descent with Barrett's oesophagus (n = 59) and those without reflux symptoms and a normal oesophagus (n =60) were recruited prospectively using endoscopic and histopathological criteria. Human leucocyte antigen class I and II typing was performed using a polymerase chain reaction sequence-specific primers method. RESULTS: The HLA-B7 allele was present in 17% (10 of 59) of patients with Barrett's oesophagus when compared with 0% (zero of 60) of controls [P = 0.0006, corrected P = 0.0171, OR = 25.67]. Subgroup analysis revealed that the HLA-B7 allele was confined almost exclusively to Indians with Barrett's oesophagus, 43% (nine of 21) vs. 0% (zero of 19) Indian controls (P = 0.0014, corrected P = 0.0406, OR = 29.64). No class II associations, protective human leucocyte antigens or extended haplotypes for disease susceptibility were identified. CONCLUSIONS: Barrett's oesophagus in Asians, particularly Indians, is strongly positively associated with HLA-B7; reinforcing a genetic component to gastro-oesophageal reflux disease. A larger sample size and different ethnic populations should be genotyped to further confirm this association and identify possible additional risk factors in the human leucocyte antigen locus.

Asian People↗

Prenatal exposure to house dust mite allergen (Der p 1), cord blood T cell phenotype and cytokine production and atopic dermatitis during the first year of life.

This study investigated the influence of prenatal exposure to house dust mite (HDM, D. pteronyssinus) on interleukin (IL)-2, interferon-gamma (IFN-gamma) and IL-4 producing CD4(+) and CD8(+) T lymphocytes in cord blood as well as on the development of sensitization and occurrence of atopic dermatitis (AD) as the first symptom of allergy during the first year of life. Dust samples (n = 22) were collected by vacuum cleaning the maternal mattress during early to mid-pregnancy. In these samples, the amount of the major HDM antigen (Der p 1) was assessed by a sensitive enzyme-linked immunosorbent assay technique (detection limit 0.004 microg/g dust). Flow cytometry was used to determine cord blood lymphocyte subtypes and to quantify the intracellular amounts of IL-2, IFN-gamma and IL-4 produced by cord blood CD4(+) helper and CD8(+) cytotoxic T lymphocytes, both spontaneously and after stimulation with phorbol-12-mirystate-13-acetate and ionomycin. Children were followed for 1 yr for the presence of symptoms associated with allergy. In addition, at the age of 1 yr specific IgE to different classical inhalant and food allergens was measured. Higher prenatal exposure to Der p 1 (>0.2 microg/g dust) was associated with a significant lower percentage of IFN-gamma producing stimulated CD4(+) T lymphocytes, compared with lower prenatal Der p 1 exposure (p = 0.03). The presence of AD during the first year of life (n = 9) was associated with an increased number of naive CD4(+) CD45RA(+) lymphocytes (p = 0.03), with an increased spontaneous IL-4 production by CD8(+) lymphocytes (p = 0.04) and with a decreased percentage of IFN-gamma producing stimulated CD4(+) lymphocytes (p = 0.04). Furthermore, exposure to HDM during pregnancy tended to be higher in mothers of children with AD during the first year of life when compared with those without AD (p = 0.08). This study shows that the level of prenatal exposure to Der p 1 influences the immune profile of cord blood T lymphocytes and the clinical outcome in early life. Therefore, the prenatal environment must be regarded as a possible early risk factors for allergic diseases in children.

Animals↗

Levels of tumour necrosis factor-alpha and IL-1alpha in newly diagnosed and multidrug resistant tuberculosis.

BACKGROUND: The pro-inflammatory cytokines tumour necrosis factor (TNF)-alpha and IL-1alpha play key roles in host defence against tuberculosis (TB) but there is little knowledge of their levels in multidrug resistant TB (MDR-TB). The aim of the present study was to investigate the levels of TNF-alpha and IL-1alpha and their relationship with the levels of T helper (CD4+), T suppressor (CD8+) and total lymphocytes (CD45+) in newly diagnosed TB (N-TB) and MDR-TB. METHODOLOGY: This study assessed 19 N-TB patients (M/F : 17/2) and 11 MDR-TB patients (M/F : 10/1). Serum TNF-alpha and IL-1alpha were assessed by ELISA. Lymphocyte expression of CD45, CD4, CD8, CD3, CD23, CD19 and CD95 were determined by flow cytometry. RESULTS: The levels of TNF-alpha, IL-1alpha, and CD4, CD4/CD8, CD45, CD19, CD23 and CD95 positive lymphocytes were lower in MDR-TB than in N-TB patients (P < 0.05). Statistically, there was a positive correlation between TNF-alpha and IL-1alpha (r = 0.92) for both MDR-TB and N-TB. For both groups, both TNF-alpha and IL-1alpha correlated with CD4+ lymphocytes (r = 0.48). TNF-alpha and IL-1alpha showed negative correlations with CD8+ lymphocytes (r = -0.81, r = -0.73) (P < 0.01) in MDR-TB patients. CONCLUSION: The lower levels of cytokines and numbers of T helper lymphocytes in MDR-TB compared with N-TB implies that the immune profiles of the two groups are different, and may be important in the natural history of the disease.

Adult↗

Concomitant vaccination against hepatitis A and typhoid fever.

BACKGROUND: The purpose of this study was to evaluate the reactogenicity and immunogenicity of a hepatitis A vaccine (Havrix-1440TM) when administered simultaneously with a Vi polysaccharide typhoid vaccine. METHODS: Two open, randomized studies were conducted using 2 and 4 treatment groups respectively, at the Clinique Notre-Dame de Grâce, Belgium (Study 1) and University Hospital of Hradec Kralové, Czech Republic (Study 2). SUBJECTS: Healthy adults aged 18-50 years were administered either both vaccines concomitantly in separate arms or a single injection of the two vaccines mixed extemporaneously (Study 1), or one injection of each vaccine alone, or the combined vaccine, or both vaccines concomitantly in separate arms (Study 2). The study measured solicited and unsolicited signs and symptoms until 28 days post-vaccination. Anti-hepatitis A and anti-Vi titers were determined in pre- and post-vaccination sera. RESULTS: The vast majority of local and general symptoms were mild to moderate and all resolved without sequelae. No serious adverse events were reported in either study. In study 1, geometric mean antibody titers (GMTs) were similar after extemporaneous syringe mixing of both vaccines (anti-Vi = 1159 EL.U/mL; anti-HAV = 302 EL.U/mL) and after concomitant vaccination (anti-Vi = 1331 EL.U/mL; anti-HAV = 367 EL. U/mL). In study 2, GMTs following vaccination with either vaccine alone, both vaccines administered concomitantly or as a combined vaccine (anti-Vi: 1307, 1247 and 942 EL.U/mL, respectively; anti-HAV: 462, 517 and 432 EL.U/mL, respectively) were not significantly different (p = .45 for anti-HAV, p = .18 for anti-Vi). Seroconversion rates were > 94.4% in all cases. CONCLUSIONS: The inactivated hepatitis A and Vi polysaccharide typhoid vaccines are safe and well tolerated when administered simultaneously (mixed or concomitant) and as a combined vaccine. Subjects seroconverted to both antigens to the same extent as the monovalent vaccines and there was no cross-interference in the immune profiles of the vaccines.

Adolescent↗

Role of temperate phage in determining lytic phage sensitivity and serotype of Vibrio cholerae.

The effect of lysogenization with five temperate phages from various sources on serotype and lytic phage sensitivity was investigated in six cultures of Vibrio cholerae of both classical and El Tor biotypes. No changes in serotype or in classical phage sensitivity in the classical biotype were observed. Four of the temperate phages were homoimmune and induced resistance to one of the El Tor typing phages, E3, thereby causing a type change in El Tor strains. The sensitivity to the other phages was not changed. In 14 natural isolates too, E3 (group III) phage resistance correlated with the presence of temperate phage. Postadsorption exclusion was found to be the mechanism of resistance involved. The fifth phage, VcA-1, had a unique immunity profile. It could infect the El Tor biotype of V. cholerae but caused no change in the host properties investigated.

Bacteriophages↗

Plasmid-containing strains of Streptococcus mutans cluster within family and racial cohorts: implications for natural transmission.

The transmission of mutans streptococci is thought to occur along familial lines based on investigations which have shown common strains within family units by using phenotypic typing methods, such as bacteriocin production and immunity profiles and serotyping. Difficulties in implementing these typing methods, coupled with conflicting interpretations of results between laboratories, led us to study the conservation of Streptococcus mutans strains within a mother-child cohort by using a genotypic marker, plasmid DNA. Plasmids (all 5.6 kilobases in size) were observed at an overall frequency of 3.3%, with a significantly different frequency in whites (1.5%) compared with blacks (6.6%). Plasmid-containing strains were significantly clustered in mother-child pairs compared with nonrelated individuals (58 versus 3.3%; P less than 0.001). Moreover, the different plasmid groups (I and II) were highly conserved within racial boundaries (P = 0.007). In those instances in which we were able to characterize distinct strains by either biotype or plasmid profile, we found that mothers harbored a more heterogeneous population of mutans streptococci than did their children. This suggested, among other possibilities, that children acquire additional strains as they approach adulthood. Alternatively, we may have been unable to detect more heterogeneity of strains in children because of quantitative differences of strains in saliva. We present collective data which show that strains of S. mutans are highly conserved within not only mothers and their children but also racial groups, suggesting vertical transmission of this organism within human populations. Moreover, we show that levels of S. mutans found in the saliva of the mother correlated with levels found in her child, demonstrating a quantitative relationship within mother-child pairs.

Family↗

Plasmacellular differentiation in extranodal marginal zone B cell lymphomas of the ocular adnexa: an analysis of the neoplastic plasma cell phenotype and its prognostic significance in 136 cases.

AIM: To determine (a) the expression of plasma cell related antigens in extranodal marginal zone B cell lymphomas (EMZL) of the ocular adnexa; and (b) the prognostic value of plasmacellular differentiation in these tumours. METHODS: A consecutive case series of 136 ocular adnexal EMZL obtained from three ocular pathology centres over 20 years was analysed retrospectively. An extensive immunohistochemical panel, including the plasma cell related antigens VS38c, CD38, CD138, multiple myeloma oncogene-1-protein (MUM1/IRF4), and CREB binding protein (CBP) was performed. EMZL were defined as "plasmacellular differentiated" on the basis of morphological features, evidence of cytoplasmic immunoglobulin, negativity for BSAP/PAX5, and expression of at least one of the investigated plasma cell related antigens. Controls included normal or hyperplastic lymphatic tissues. Detailed clinical data were collected for most patients, and compared with the results of immunohistochemistry. The end points considered for statistical analysis were development of local tumour recurrence, development of systemic disease, and lymphoma related death. RESULTS: 57 (42%) of the 136 ocular adnexal EMZL showed a plasmacellular differentiation; 45 of these plasmacytoid cases were primary tumours. In contrast with most admixed normal plasma cells, which displayed co-expression of MUM1/IRF4, Vs38c, CD38, CD138, and CBP, the plasmacellular differentiated EMZL tumour cells demonstrated co-expression of all five plasma cell related antigens in only six of 57 (11%) plasmacellular differentiated ocular adnexal EMZL. The most commonly expressed plasma cell related antigen was MUM1/IRF4, immunoreactivity being seen in 56/57 (98%) plasmacellular differentiated EMZL examined. Although the association of plasmacellular differentiation in primary ocular adnexal EMZL and disseminated disease was statistically significant on univariate analysis (p = 0.042), this was weaker on multivariate analysis. CONCLUSION: Plasmacellular differentiated tumour cells in EMZL demonstrate an aberrant immune profile for plasma cell related antigens when compared with normal plasma cells. On multivariate analysis, plasmacellular differentiation in ocular adnexal EMZL was not significantly associated with local recurrence, the development of systemic disease, or with lymphoma related death.

ADP-ribosyl Cyclase↗

Immunohistological characterisation of tumour infiltrating lymphocytes in melanocytic skin lesions.

BACKGROUND: Although the presence of tumour infiltrating lymphocytes (TIL) is a constant feature in melanomas, their immunophenotypic characterisation is still incomplete. We hypothesise that the transition from normal skin to benign naevi (BN) to melanocytic dysplastic naevi (MDN) to radial growth phase cutaneous malignant melanoma (RGP-CMM) to vertical growth phase cutaneous malignant melanoma (VGP-CMM) is associated with alterations in TIL. This study attempted to test this hypothesis and to characterise TIL in the melanocytic skin lesions. METHODS: In total, 74 lesions (12 BN, 12 MDN, 13 RGP-CMM, 26 VGP-CMM, and 11 metastatic melanomas) were examined using immunoperoxidase staining methods and antibodies targeting leukocyte common antigen (LCA+), T (CD3+) and B (CD20+) lymphocytes, and resting cytotoxic T cells (TIA-1+). RESULTS: Histologically, the transitions from normal skin to BN to MDN to RGP-CMM to VGP-CMM was associated with a gradual increase in the numbers of TIL (total, parenchymal, stromal, perivascular, and epidermal TIL, as well as TIL at the base of the lesions). The numbers of TIL were higher at the stroma than at the parenchyma. Similarly, immunostaining revealed that these transitions were associated with a gradual increase in the staining values (staining intensity, percentage of positive cells, and immunoreactivity score) for LCA+, CD20+, CD3+, and TIA-1+cells. The number of CD3+ cells was higher than that of CD20+ cells. All these differences between the normal skin and the lesional ones reached statistical significance (p<0.01). The majority of CD3+ cells were TIA-1+ T cells with cytotoxic potential. Compared with primary melanomas, there was a decrease in TIL in metastatic melanomas. CONCLUSIONS: The gradual increase in TIL during melanoma tumorigenesis may reflect increased antigenicity of the tumour cells. Although both humoral and cell mediated immunity are involved in melanomagenesis, the latter seems to have the major role. The immune profile of MDN suggests their intermediacy between BN and CMM.

Analysis of Variance↗

Dendritic cell vaccination in medullary thyroid carcinoma.

PURPOSE: Prognosis and treatment effectiveness for medullary thyroid carcinoma (MTC) are strictly related to tumor stage. Palliative treatment options show no significant benefit. A promising treatment approach for human cancer is based on the vaccination of autologous dendritic cells (DCs). EXPERIMENTAL DESIGN: The objective of this study was to evaluate the effectiveness of DC vaccines in MTC patients. Therefore, we generated autologous tumor lysate-pulsed DCs from 10 patients suffering from advanced MTC for repeated vaccination. Mature DCs were derived from peripheral blood monocytes by using CD14 magnetic bead selection and subsequent culture in the presence of granulocyte macrophage colony-stimulating factor, interleukin 4, and tumor necrosis factor alpha with or without addition of IFN-gamma. DCs were loaded with tumor lysate and further injected into a groin lymph node. Toxicity, tumor marker profile, immune response, and clinical response were determined. RESULTS: Vaccination was well tolerated and induced a positive immunological response in all of the tested patients as evaluated by in vivo delayed-type hypersensitivity reactivity or in vitro intracytoplasmic IFN-gamma detection assay. Three patients had a partial response, 1 patient presented a minor response, and 2 patients showed stable disease. The remaining 4 patients had progressive disease. CONCLUSIONS: These data provide strong evidence that vaccination with tumor-lysate pulsed DCs results in the induction of a specific immune response in patients suffering from MTC. Objective clinical responses could be observed even for far-advanced disease. Therefore, we suggest that MTC is particularly suited for DC-based immunotherapy.

Adult↗

CpG motifs as possible adjuvants for the treatment of allergic diseases.

DNA containing unmethylated CpG motifs and synthetic oligodeoxynucleotides derived thereof (CpG ODN) have intensively been investigated for their immunostimulatory properties in the recent past. CpG ODN were shown to induce strong Th1 immune responses in mammals. The downregulation of the antigen-driven Th2 response of type I allergies represents one important therapeutic goal of specific immunotherapy (SIT). Hence, CpG ODN represent promising substances which support the modification of the pathogenic Th2 immune profile toward a Th1 profile when used as adjuvants for SIT. This article discusses how the use of CpG ODN in immunotherapeutics could improve the treatment of type I allergy.

Adjuvants, Immunologic↗

A study on delayed hypersensitivity aspects of immune response in patients with carcinoma of bronchus in relation to radiotherapy.

Results of a preliminary study on the delayed hypersensitivity aspects of immune response in 45 patients with carcinoma of bronchus revealed by sequential skin testing are presented. Short-term prognosis and the immune reactivity thus studied appear to be well correlated. Anergy before treatment and allergy changing to anergy following radiotherapy tend to be associated with grave prognosis and conversely persistently allergic patients fare better at least on short-term prognosis. Contrary to the usual impression that radiations are immunodepressant, this study reveals increased skin tests reactivity following radiotherapy in 7 out of 17 immunocompetent patients. Recent literature on human and animal studies appear to support this phenomenon of increased immune reactivity in certain situations following radiotherapy and chemotherapy. The few publications are reviewed. A much more elaborate controlled in vivo and in vitro study is now underway to reveal the immune profile of patients with cancer particularly in relation to radiotherapy.

Adult↗

T lymphocyte subsets and function in the peripheral blood of patients with urological cancer.

The phenotypic distribution and immune reactivity of T lymphocyte subpopulations from peripheral blood of 50 patients with urological cancer were determined. Included were 36 patients with bladder transitional cell carcinoma, 7 patients with renal cell carcinoma and 7 patients with prostatic carcinoma. Thirty-eight age-matched patients with benign urological disease served as controls. A depression in immune competence was found in the group of male patients with infiltrating bladder cancer. In more than 50% of the patients with infiltrating bladder carcinoma, the T helper (CD4) subset was reduced with a concomitant inversion in the CD4/CD8 ratio and impairment in the T cell function as determined by the ability to proliferate upon phytohemagglutinin and concanavalin stimulation. Patients with superficial bladder carcinoma, as well as those with renal cell carcinoma had an immune profile similar to that of the control group. The group of patients with prostatic carcinoma had higher mean CD4/CD8 ratios than the control group, resulting from decreased suppressor/cytotoxic cells. Our results have indicated that the characterization of T cell subset and lymphocyte activity correlated well with the histopathologic state of patients with bladder carcinoma. Thus, the determination of the CD4/CD8 ratio may prove a valuable method for monitoring patients with bladder carcinoma, in addition to serial urine cytology, random urothelial biopsies and flow cytometry.

Adenocarcinoma↗