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Biomedical subjects

N Rautonen

Publications and source records attributed to N Rautonen.

At least 19 recordsLinked to original sources
PubMed2000

Immunity to Chlamydia pneumoniae induced by vaccination with DNA vectors expressing a cytoplasmic protein (Hsp60) or outer membrane proteins (MOMP and Omp2).

Immune responses induced by intramuscular DNA immunization with Chlamydia pneumoniae genes coding for the major outer membrane protein (MOMP), cysteine-rich outer membrane protein 2 (Omp2) or the heat shock protein 60 (Hsp60) were studied. BALB/c mice were vaccinated intramuscularly three times at 3-week intervals and challenged intranasally 2 weeks after the last injection. Immunization with pmomp or phsp60 showed 1.2-1.5 log reduction in the mean lung bacterial counts after the challenge. Specific antibodies were detected only in sera of the mice immunized with pomp2 and phsp60. Although immunization with pomp2 resulted in a strong serum antibody response against Omp2 protein, it failed to protect the mice. Immunization with any of the three vaccines did not reduce the severity of histologically assessed pneumonia, but resulted in significantly higher lymphoid reaction in the lung indicating immunological memory.

Animals↗
PubMed2000

Autoimmunity to glutamic acid decarboxylase in patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED).

Antibodies to glutamic acid decarboxylase (GAD) occur frequently in patients with APECED, although clinical insulin-dependent diabetes mellitus (IDDM) is seen only in a subgroup of the patients. We studied the cellular immunity to GAD, antibodies to GAD and their association with the HLA DQB1 risk alleles for IDDM in patients with APECED. Proliferation responses to GAD were enhanced in the patients with APECED when compared with the control subjects (P = 0.004), but autoimmunity to GAD was not associated with IDDM in APECED. The levels of interferon-gamma (IFN-gamma) secreted by GAD-stimulated T cells were higher in the patients than in control subjects (P = 0. 001). A negative correlation (r = - 0.436, P = 0.03) existed between the antibody levels and the stimulation indices (SIs) to GAD. In 14 non-diabetic patients no difference in insulin secretion was observed in intravenous glucose tolerance test (IVGTT) between the patients with and without T cell reactivity to GAD. We conclude that cellular immunity to GAD detected as T cell proliferation response to GAD or IFN-gamma secretion by GAD-stimulated T cells was frequent in patients with APECED (69%) and was not restricted to the patients with clinically detectable beta-cell damage.

Adolescent↗
PubMed2000

Acquired immunity to Chlamydia pneumoniae is dependent on gamma interferon in two mouse strains that initially differ in this respect after primary challenge.

The role of gamma interferon (IFN-gamma) in a Chlamydia pneumoniae mouse model was studied by in vivo neutralization in two inbred mouse strains. During primary C. pneumoniae infection, neutralization of IFN-gamma increased both the numbers of bacteria and the pneumonia score in the lungs of C57BL/6 mice but not BALB/c mice. During reinfection, the bacterial counts in the lungs were increased by IFN-gamma neutralization in both mouse strains. Thus, the effect of IFN-gamma neutralization was dependent on the genetic background in primary infection. However, IFN-gamma appeared to be equally important in both mouse strains during reinfection.

Animals↗
PubMed1999

Mononuclear cell subpopulations in preterm and full-term neonates: independent effects of gestational age, neonatal infection, maternal pre-eclampsia, maternal betamethason therapy, and mode of delivery.

Blood samples from 29 preterm (24-32 weeks of gestation) and 21 full-term (37-42 weeks of gestation) neonates were analysed for surface markers of lymphocyte subtypes and macrophages, and the effects of gestational age, neonatal infection, maternal pre-eclampsia, maternal betamethason therapy and mode of delivery were assessed with multiple regression analysis. Gestational age alone had few independent effects (increase in CD3+, CD8+CD45RA+, and CD11alpha+ cells, and decrease in CD14+, HLA-DR- cells) during the third trimester on the proportions of the immune cell subtypes studied. Neonatal infection and mother's pre-eclampsia had the broadest and very opposite kinds of effects on the profile of immune cells in the blood. Infection of the neonate increased the proportions of several 'immature' cells (CD11alpha-CD20+, CD40+CD19-, and CD14+HLA-DR-), whereas mother's pre-eclampsia decreased the proportions of naive cell types (CD4+CD8+, CD5+CD19+). In addition, neonatal infection increased the proportion of T cells (CD3+, CD3+CD25+, and CD4+/CD8+ ratio, and CD45RA+ cells), while maternal pre-eclampsia had a decreasing effect on the proportion of CD4+ cells, CD4+/CD8+ ratio, and proportions of CD11alpha+, CD14+ and CD14+HLA-DR+ cells. Maternal betamethason therapy increased the proportion of T cells (CD3+) and macrophages (CD14+, CD14+HLA-DR+), but decreased the proportion of natural killer (NK) cells. Caesarean section was associated with a decrease in the proportion of CD14+ cells. We conclude that the 'normal range' of proportions of different mononuclear cells is wide during the last trimester; further, the effect of gestational age on these proportions is more limited than the effects of other neonatal and even maternal factors.

Antigens, CD↗
PubMed1999

Depletion of CD8+ cells abolishes memory in acquired immunity against Chlamydia pneumoniae in BALB/c mice.

The importance of T cells in Chlamydia pneumoniae infection in mice was assessed by comparing wild-type BALB/c mice with nude mice and mice depleted in vivo of either CD4+ or CD8+ T cells. Whereas wild-type mice cleared the primary infection in 3 weeks, nude mice were only able to restrict the infection and could not clear it during the observation period of 56 days. Nude mice exhibited a greater number of macrophages in their lungs and the pulmonary cells secreted a higher level of tumour necrosis factor-alpha (TNF-alpha) than wild-type mice. Depletion of CD4+ cells did not change the overall infection kinetics of the primary infection. However, depletion of CD8+ cells resulted in a slightly impaired clearance of the bacteria in the late stages of primary infection. To assess the role of the two T-cell subsets in the acquired immunity that develops during primary infection in wild-type BALB/c mice, in vivo depletions were performed during reinfection. Prior to reinfection, immunocompetent wild-type mice were infected and natural immunity was allowed to form. During reinfection, depletion of CD4+ cells did not have any effect on infection kinetics, whereas depletion of CD8+ cells abolished the protection, reverting the infection kinetics and bacterial load to the same levels found in wild-type mice during primary infection. These results show that T cells are necessary for clearing C. pneumoniae infection in mice. Furthermore, whereas neither of the two main T-cell subsets, separately, were essential for clearance of primary infection, the induced protective immunity was strongly CD8 dependent.

Animals↗
PubMed1998

Local immune responses to Chlamydia pneumoniae in the lungs of BALB/c mice during primary infection and reinfection.

Cell-mediated immune (CMI) responses play a major role in protection as well as pathogenesis of many intracellular bacterial infections. In this study, we evaluated the infection kinetics and assessed histologically the lymphoid reactions and local, in vitro-restimulated CMI responses in lungs of BALB/c mice, during both primary infection and reinfection with Chlamydia pneumoniae. The primary challenge resulted in a self-restricted infection with elimination of culturable bacteria by day 27 after challenge. A mild lymphoid reaction characterized the pathology in the lungs. In vitro CMI responses consisted of a weak proliferative response and no secretion of gamma interferon (IFN-gamma). The number of lung-derived mononuclear cells increased substantially during the primary infection; the largest relative increase was observed in B cells (B220(+)). After reinfection, the number of lung-derived mononuclear cells increased further, and the response consisted mainly of T cells. The reinfection was characterized in vivo by significant protection from infection (fewer cultivable bacteria in the lungs for a shorter period of time) but increased local lymphoid reaction at the infection site. In vitro, as opposed to the response in naive mice, acquired immunity was characterized by a strongly Th1-biased (IFN-gamma) CMI response. These results suggest that repeated infections with C. pneumoniae may induce Th1-type responses with similar associated tissue reactions, as shown in C. trachomatis infection models.

Animals↗
PubMed1998

Expansion of a novel pulmonary CD3(-) CD4(+) CD8(+) cell population in mice during Chlamydia pneumoniae infection.

A new pulmonary T-cell-like lymphocyte population with the phenotype CD3(-) CD4(+) CD8(+) was discovered in mice. CD4(+) CD8(+) but CD3(+) cells among murine intestinal intraepithelial lymphocytes have previously been described. We describe herein a dramatic expansion of the CD3(-) CD4(+) CD8(+) cell population in response to experimental respiratory infection. After intranasal Chlamydia pneumoniae infection, CD4(+) CD8(+) cells became transiently the dominant lymphocyte type (maximum of 87% of all lymphocytes) in the lungs of NIH/S mice but remained virtually undetectable in spleen and blood. The enrichment of these cells was not a C. pneumoniae-specific event, since infection of NIH/S mice with influenza A virus also resulted in an increase in the number of CD4(+) CD8(+) cells (maximum of 42% of all lymphocytes). In addition to outbred NIH/S mice, two other mouse strains were studied: BALB/c (H-2(d)) and C57BL/6 (H-2(b)). C. pneumoniae-infected BALB/c mice responded with an intermediate increase in the number of CD4(+) CD8(+) cells in lungs, whereas C57BL/6 mice did not respond. The double-positive CD4(+) CD8(+) cells lacked a major part of the T-cell receptor complex, being both CD3(-) and TCR alpha beta-. However, when they were stimulated in vitro with a T-cell mitogen, they responded by proliferation but did not secrete gamma interferon. The dramatic expansion of this cell population at the infection site suggests an active role for them in respiratory infection, but the specification of this requires further study.

Animals↗
PubMed1997

Interleukin-10 production by cord blood mononuclear cells.

The production of IL-10 by newborns has not been studied in much detail. We analyzed the IL-10 production by, and surface marker distribution of, cord blood mononuclear cells (n = 47); adult peripheral blood mononuclear cells (n = 30) were used as controls. Both the baseline (0.79 versus 1.54 ng/mL, p = 0.001) and lipopolysaccharide-stimulated (1.20 versus 2.88 ng/mL, p = 0.003) levels of IL-10 production were significantly lower in newborns than in adults. No significant differences were observed after stimulation with concanavalin A. Both cord blood and adult CD19+CD5+ cells were able to produce IL-10; however, the level of production was only an average of 16% of the total stimulated IL-10 production by unfractionated cells, indicating that CD5+ B cells are not the primary source of IL-10 in either adults or newborns. In newborns, the proportion of naive CD4+CD45RA+ cells was inversely correlated with IL-10 response to lipopolysaccharide (r = -0.49, p = 0.004) indicating a role for maturing T cells in neonatal IL-10 production; the number of macrophages was not significantly correlated with IL-10 response (r = 0.30, p = 0.10). In contrast, in adults IL-10 production correlated with the number of macrophages (r = 0.49, p = 0.01) but not CD4+CD45RA+ cells (r = -0.06, p = 0.77). We conclude that newborns produce less IL-10 than adults; the primary cells of origin and the regulatory mechanisms may be different from those observed in adults.

Adult↗
PubMed1994

HIV type 1 Tat protein induces immunoglobulin and interleukin 6 synthesis by uninfected peripheral blood mononuclear cells.

Tat is a potent trans-activating protein encoded by the HIV genome. It is essential for viral replication, but has pleiotropic effects on host cells as well. We demonstrated that exogenous recombinant Tat increases immunoglobulin (Ig) and interleukin 6 (IL-6) production in vitro by normal uninfected peripheral blood mononuclear cells by 100-500%. The optimal Tat concentration was 100 ng/ml, but even a low concentration of 1 ng/ml induced a response in most subjects. The observed induction was inhibited by monoclonal anti-Tat antibodies and 2,3-dimercapto-1-propanol. Both anti-IL-6 antibodies and IL-6 antisense oligonucleotides inhibited Tat-induced IgG and IgA synthesis to some degree, whereas induction of IgM appeared to be independent of IL-6. We conclude that Tat can function in vitro in the absence of any other viral structures and induce Ig and IL-6 production; the clinical significance of these findings remains as yet undetermined.

Adult↗
PubMed1992

Low number of antibody producing cells in patients with sickle cell anemia.

B cell function is impaired in patients with sickle cell anemia. Although the number of surface IgM positive cells was similar in sickle cell patients and controls, in vitro spontaneous IgM, and PWM stimulated IgA, IgM, and IgG synthesis was significantly lower in the patients than in controls. The number of PWM induced and antigen specific immunoglobulin producing cells after immunization with Pneumovax, containing 21 serotypes of Streptococcus pneumoniae, was about 100-fold lower in the patients as compared with controls. Finally, the ability of the patients' peripheral blood mononuclear cells to proliferate in response to mitogens (PWM, SAC, PHA) was diminished. Because of the observed impairments in both nonspecific and antigen specific immunoglobulin synthesis and cell proliferation assays in the patients, we determined serum concentrations of IL-4 and IL-6, two cytokines associated with antibody production. IL-4 concentrations appeared low in sickle cell patients, and correlated with that of serum IgM. We hypothesize that B cell maturation in sickle cell patients is arrested at an IL-4 dependent stage.

Adult↗
PubMed1992

A screening test for the detection of anti-HIV-1 IgA in young infants.

A simple dot blot screening test for anti-HIV-1 IgA in infant sera was developed using recombinant HIV proteins. Ten control infants, 19 uninfected infants of seropositive mothers and 12 HIV culture positive infants were studied at 3 month and 18 month time points. Prior to IgG depletion of the serum samples, 11/12 (92%) of the infected infants, 2/19 (11%) of the uninfected and none of the control infants were anti-HIV IgA positive at 3 months of age. After depletion, no anti-HIV IgA antibodies could be detected in the samples from uninfected infants, whereas the antibodies persisted in all 11 samples from the infected infants, resulting in sensitivity and specificity of 91.7% (95% confidence limits 59.8-99.6%) and 100% (79.1-100%) respectively. The assay might prove useful in the early diagnosis of HIV infection and can be performed at a fraction of the cost of commercially available western blot strips.

HIV Antibodies↗
PubMed1991

Allotype-associated differences in concentrations of human IgG subclasses.

The concentrations of seven immunoglobulin isotypes (IgA, IgE, IgM, IgG1, IgG2, IgG3, and IgG4) were measured in the sera of 207 Finnish blood donors, and they were allotyped with anti-Gm antibodies: anti-f, anti-a, anti-x, and anti-n. The above population could be divided into 12 phenotypes, and significant differences in isotype concentrations between different phenotypes were observed. They are best explained by postulating that the following alleles of different loci are associated with a high concentration of the product of the locus: a(x)-IgG1, n-IgG2, b-IgG3, and perhaps 4b-IgG4. The following concentration differences between the low and the high homozygotes were found: IgG1, 1.2-fold; IgG2, 1.5-fold; and IgG3, 2.6-fold. No significant allotype-associated differences in the concentrations of IgA, IgM, or IgE could be detected.

Alleles↗
PubMed1991

Gm allotypes influence the production of IgG3 but the effect is age-dependent.

Serum concentrations of IgG3 were found to be higher in Gm-f-positive (= b-positive) than in f-negative individuals except in young children. Young children aged 3-4 months had a mean concentration of 0.24 g/l of IgG3 regardless of allotype. The concentration gradually rose with age in f-positive individuals to a geometric mean of 0.56 g/l in adults but it remained essentially unchanged in f-negative people. A corresponding allotype effect was seen in influenza-specific antibody responses. While the total IgG response (mainly IgG1) was equally strong in f-positive and in f-negative patients, f-positive (= b-positive) patients produced more IgG3 antibodies than f-negative patients. The difference between geometric mean values of opposite homozygotes (f/f versus f-negative) was 2.3-fold (p = 0.0113). This finding indicates that the b-positive gamma-3 allele is more productive than the g-positive allele.

Adult↗