Search PubMed⌕ Search

Biomedical subjects

A Coutinho

Publications and source records attributed to A Coutinho.

At least 379 records · Page 21Linked to original sources
PubMedDate not supplied

A compartment of effector helper and suppressor T cells in the normal mouse thymus.

We have recently described an autonomously activated set of T cells in the spleens of normal and "antigen-free" mice which display effector T helper (TH) or T suppressor (TS) activities; we describe here an intrathymic effector T-cell compartment which directly helps or suppresses B-cell responses and appears to be distinct from the peripheral set of effector cells. Splenic effector T cells do not represent recent thymic migrants (because adult thymectomized mice have unaltered levels of effector TH and TS cells in the spleen), nor do intrathymic effector T cells represent circulating peripheral T cells (since thymic effector T cells are B2A2+, while splenic effector T cells are B2A2-). Furthermore, effector TH cells within the two compartments exert differential effector activities: splenic effector TH cells induce B cells to both proliferation and maturation, while thymic effector TH cells are defective in activating B-cell maturation. The present findings extend our studies on "natural" lymphocyte activities in the normal immune system, revealing the existence of two apparently distinct effector T-cell compartments. The potential significance of the intrathymic set of effector cells in repertoire selection is considered.

Animals↗
PubMedDate not supplied

Parasitic load increases and myocardial inflammation decreases in Trypanosoma cruzi-infected mice after inactivation of helper T cells.

In order to characterize the role played by CD4+ T lymphocytes in the immunopathology of acute Trypanosoma cruzi infection, we compared the numbers of blood and tissue parasites and the heart inflammatory reaction in normal and anti-CD4 antibody-treated C3H mice. Treatment of mice with anti-CD4 mAb during acute infection markedly inhibited T-helper-cell-dependent activities, as measured by peritoneal macrophage activation and immunoglobulin secretion by splenic B lymphocytes. After in vivo inactivation of helper T cells, the number of blood and tissue parasites significantly increased, while the inflammatory cellular infiltrates of heart muscles diminished. Our results indicate that CD4+ T lymphocytes play a dual role in the immunopathology of acute experimental Chagas' disease.

Animals↗
PubMedDate not supplied

Natural lymphocyte activation in postnatal development of germ-free and conventional mice.

The degree of activation of B and T cells in the developing spleen during postnatal life was studied in germ-free (GF) and specific-pathogen-free (SPF) BALB/c mice of the same breeding stock. We found that the progeny of GF mothers up to 3 weeks of age contain higher numbers of activated splenic cells than baby SPF mice, thus suggesting qualitative differences in maternally-derived antibodies. This "advantage" of GF mice is also indicated by an anticipated maturation of the splenic lymphoid compartment and is reflected in higher frequencies of B and T lymphocytes in adult life. In both kinds of mice, the frequency of activated cells is very high at birth and then declines, reaching minimal values by 4 weeks of age. Later, activated B cells increase sharply in SPF mice, suggesting polyclonal activation mediated by bacterial products. Results are discussed on the basis of the mutual influences between B and T cells in the establishment of a functional network.

Animals↗
PubMedDate not supplied

Immune networks: getting on to the real thing.

After some ten years of faltering development, the network approach in immunology is finally heading toward steady ground. At a recent international workshop (*), experimentalists and theoreticians discussed some of the latest developments, including an impressive array of novel results and applications to fundamental properties of biological immune networks: connectivity, patterns of dynamic activity, ontogenesis, and tolerance.

Animals↗
PubMedDate not supplied

Expression of VH11-gene family in hybridoma collections from peritoneum and spleen: differential correlation with BrMRBC reactivity.

Hybridoma collections from spleen or peritoneal cells of newborn or adult individuals were screened by RNA hybridization for expression of the VH11-gene family using a V-region probe VCP12, which encodes anti-BrMRBC antibodies. No VH11 expression was observed in hybridomas derived from newborn spleen cells in either BALB/c, NZB or (CBA/N x BALB/c) F1 mice (0/93). Adult NZB and BALB/c spleen cell collections contained only one hybridoma expressing VH11 (1/242). Interestingly, however, the VH11-positive hybridoma showed no anti-BrMRBC reactivity, while one anti-BrMRBC clone in the same collection expressed a Q52 VH gene. In contrast, hybridomas derived from peritoneal cells showed an absolute correlation between expression of VH11 genes and anti-BrMRBC reactivity (15/32). The high expression in the peritoneal cavity of such cells is likely the result of local positive selection.

Animals↗
PubMedDate not supplied

Simple developmental programs of gene expression and cellular composition of lymphoid organs at the origin of natural tolerance.

Self-tolerance is acquired in the embryonic/perinatal period, but new lymphocytes (that will have to distinguish between self and nonself) continue to be produced throughout life, after both self and nonself are present. This makes it impossible for natural tolerance to rely on recessive mechanisms. Recent observations on "dominant tolerance" have led to the hypothesis that natural tolerance is established as a consequence of simple developmental programs for gene expression and cellular composition of primary lymphoid organs. In development, the cellular composition of the thymus is predominantly epithelial, allowing for the positive selection and activation of "high avidity" self-reactive T cells that are not deleted because antigen presentation by haemopoietic cells is limiting. Such T cells, activated in that environment, display effector functions of a regulatory type that are maintained in the periphery upon restimulation by tissue peptides shared with the thymic epithelium. Recent thymic emigrants with specificity for tissue-specific antigens that are absent from the thymus will first encounter their ligands in the context of the "regulatory cell" recognition of ubiquitous peptides and are thus recruited into similar regulatory activities. In contrast, thymic emigrants with specificity for nonself antigens (absent during the perinatal period) are not activated intrathymically, reach the periphery as resting cells, and move out of the time window of susceptibility to functional recruitment. These will react "de novo" upon encounter of the respective antigens and will acquire the class of effector functions determined by the peripheral microenvironment in which they are activated. This strategy, which explains the thymic dependence of peripheral tissue-specific tolerance, may be re-enforced by developmental restrictions in cytokine gene expression, and it will ensure the establishment and maintenance of T-cell tolerance through the dynamic storage of a distributed memory of the embryonic self. B lymphocytes that are produced in the embryonic/perinatal period characteristically rearrange and express a few V-genes very predominantly. These V-genes encode antibodies with unique properties of "connectivity" to other V-regions, making it possible to establish a network that limits clonal expansions and/or terminal differentiation to antibody production. Self-reactive B cells are thus recruited into such a network which, by contributing to the molecular environment of the body and to the selection of emergent repertoires, leads to deletion of connected cells and to the "normalization" of the adult antibody repertoires. Natural autoantibody repertoires in the adult are thus recursively maintained, stable and continuously adjusted to the thresholds of single cell deletion and to the alterations in the body composition. The activity of self-specific regulatory T cells contributes to limiting clonal expansion and inhibiting somatic mutation of self-reactive B cells. This model explains a number of observations that were not included in the "clonal" and "recessive" tolerance views, and offers suggestions on mechanisms in physiological autoimmunity and pathology.

Animals↗
PubMedDate not supplied

Histological evidence for adulticidal effect of low doses of diethylcarbamazine in bancroftian filariasis.

The ability of diethylcarbamazine (DEC) to kill adult Wuchereria bancrofti worms was evaluated by examining lymphatic nodules formed after treatment with 4 different treatment schedules of 193 males living in the endemic area of Greater Recife, Brazil. Lymphatic nodules appeared in the spermatic cord or upper extremities in 43 of 138 microfilaraemic individuals, in 3 of 30 amicrofilaraemic patients with filarial disease manifestations, and in 1 of 25 asymptomatic amicrofilaraemic residents of the endemic area treated with DEC. Fourteen of these nodules were surgically removed 10-150 d after the start of treatment. Regardless of the DEC dosage and schedule used, all nodules contained damaged and degenerating adult worms. An exuberant granulomatous process with large numbers of eosinophils and progressive fibrosis gradually developed around the dead parasites. The mechanism(s) by which DEC killed adult W. bancrofti could not be determined.

Adolescent↗
PubMedDate not supplied

Occurrence of living adult Wuchereria bancrofti in the scrotal area of men with microfilaraemia.

To determine the frequency with which living adult Wuchereria bancrofti can be detected by ultrasound in the scrotal area of men with filarial infection, we used a 7.5 MHz transducer to perform weekly ultrasound examinations on 100 microfilaraemic men (18-34 years old) from Greater Recife, Brazil. The peculiar pattern of movement that characterizes the adult worm image on ultrasound (the filaria dance sign) was detected in the lymphatic vessels of the spermatic cord in 80 men (bilaterally in 29 men). Among 20 men with no filaria dance sign, the geometric mean microfilarial density was 68/mL, compared with 238/mL and 775/mL among those with unilateral and bilateral filaria dance signs, respectively (P = 0.0001). The lymphatic vessels of the spermatic cord appear to be a common, and perhaps the principal, site of adult W. bancrofti in men with asymptomatic microfilaraemia. Studies are needed to define the relationship between the presence of filarial worms in the scrotal area and the development of filaria-associated morbidity.

Adolescent↗
PubMedDate not supplied

From the mechanisms of lymphocyte activation to internal activity in the immune system.

The principles of lymphocyte activation were summarized for all three sets of immunocompetent cells: B cells, cytotoxic cells and helper T lymphocytes. They were then used to derive the basic mechanisms and specificities which drive internal activity in the normal immune system and which select available antibody repertoires. It was postulated that "natural antibodies" are induced by "natural helper cells" and are selected on the basis of their idiotypic profiles, which are complementary to available T-helper-cell repertoires. "Natural idiotypes" would then carry idiotopes similar to MHC epitopes, the predominant germ-line specificity of T-cell repertoires.

Animals↗
PubMedDate not supplied

Anti-Ia.7 antibodies recognize a "major" idiotype of the anti-TNP antibody response in BALB/c mice.

Monoclonal antibodies to Ia.7 were used, in parallel with other antibodies specific for "major" and "private" idiotopes, to define idiotypic profiles in the primary anti-trinitrophenyl plaque forming cell (PFC) response of BALB/c and C57BL/6 mice. A considerable fraction (25%) of BALB/c but not C57BL/6 PFC were inhibited by anti-Ia.7 antibodies, which failed to inhibit PFC with other paratopic specificities. These results suggest idiotypic mimicry between "major" antibody clonotypes and MHC determinants which might play a role in the selection of antibody repertoires.

Animals↗
PubMedDate not supplied

T-cell-dependent modulation of the polyclonal B-lymphocyte responses in normal spleen cell cultures stimulated by lipopolysaccharide.

The in vitro polyclonal B-cell proliferative and plaque-forming cell (PFC) responses to the T-independent (TI) mitogen lipopolysaccharide (LPS) are increased by the addition of normal syngeneic splenic T cells. Normal irradiated Lyt-2- T cells also alter the IgG subclass distribution from the typical predominance of IgG3 and IgG2b PFC to the appearance of IgG1, IgG2a and IgA PFC in T-cell-depleted spleen cell (SC) cultures. Furthermore, secondary LPS blast cultures yield increased PFC responses when co-cultured which syngeneic fresh normal T cells which, even in the absence of mitogen, induce PFC responses in such activated B cells. As LPS blasts induce normal syngeneic T cells to proliferate and significant numbers of L3T4+ blast cells are found in LPS-stimulated normal spleen cell cultures, we conclude that T cells actively participate in the regulation of these responses. The significance of these findings for the regulation of TI responses in vivo by "autoreactive" T cells is considered.

Animals↗
PubMedDate not supplied

Establishment of idiotypic helper T-cell repertoires early in life.

Immunoglobulin variable-region (V) genes, it is now recognized, do not encode specific receptors for T lymphocytes. Classical observations on T-cell expression of immunoglobulin idiotypes had remained unexplained until recent experiments showed that immunoglobulin idiotypes expressed by T lymphocytes in normal mice are absent in cells of the same specificity isolated from donors whose B-cell system has been suppressed by administration of anti-mu antibodies from birth. This observation provided evidence for the 'learning' of T-cell idiotypes from the B-cell/antibody system and, therefore, for the importance of idiotypic network interactions in the selection of available lymphocyte repertoires before antigenic challenge. Previously described influences of B cells and/or antibodies on the T-helper (Th) cell compartment would appear to operate at the level of clonal repertoires by complementarities with defined immunoglobulin idiotypes. Other authors, however, had previously shown the striking stability of T-cell idiotype expression in chimaeric animals reconstituted with T and B cells originating from donors showing differential idiotype expression. We have now investigated this apparent discrepancy and present here results demonstrating that immunoglobulin-dependent selection of T-cell (idiotypic) repertoires only operates for the first 3 weeks of life.

Age Factors↗