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A Bandeira

Publications and source records attributed to A Bandeira.

At least 19 recordsLinked to original sources
PubMed1992

Transplantation tolerance is unrelated to superantigen-dependent deletion and anergy.

C57BL/6 (B6; I-E-, Mls-2b) nude mice, reconstituted at birth with thymic epithelium (TE) from BALB/c (BA; I-E+, Mls-2a) day 10 embryos (E10), permanently accepted BALB/c skin, when grafted as adults. T-cell receptor repertoire analyses in the periphery of these mice revealed no difference in frequencies of I-E/superantigen-reactive T-cell receptor V beta families, as compared to chimeras constructed with syngeneic B6 E10 TE. T lymphocytes bearing V beta 3, V beta 5, and V beta 11 T-cell receptors, from either allogeneic or syngeneic TE chimeras, responded equally well to in vitro receptor-dependent stimulation. Similar results were obtained with nude mice reconstituted at birth with E14 thymuses, already colonized by hemopoietic cells. These observations indicate that neither TE cells nor the progenies of hemopoietic precursors that colonize the thymus up to E14 express or functionally present the superantigens addressed here; it follows that tolerance to skin grafts and superantigen-related T-cell deletions are unrelated phenomena.

Animals↗
PubMed1992

Thymic epithelium induces neither clonal deletion nor anergy to Mls 1a antigens.

Grafting of thymic anlagen from day-10 DBA/2 (H-2d; Mls-1a) embryos to newborn athymic BALB/c (H-2d; Mls-1b) mice leads to reconstitution of T cell populations in the recipients. Analysis of adult chimeras shows that their V beta T cell receptor (TcR) repertoires, particularly V beta 6 and V beta 8.1, do not significantly differ in most animals (10 out of 13) from those scored in control chimeras that received syngeneic thymic anlagen. In all cases analyzed, such Mls-1a-reactive T cells could be stimulated at levels comparable to control responses, both in vitro and in vivo. The few cases in which Mls-1a reactive V beta TcR were reduced seem to reflect the variability in TcR V beta repertoires found in this experimental system. In contrast, BALB/c mice, injected at birth with DBA/2 spleen cells show a marked, albeit variable, reduction in the frequencies of V beta 6- and V beta 8.1-bearing CD4+ T cells, and lower frequencies of Mls-1a-reactive T cells in limiting dilution analyses. It appears, however, that V beta 6- and V beta 8.1-bearing T cells remaining in these mice are functionally competent. We conclude that Mls-1 antigens are not expressed by thymic epithelium.

Animals↗
PubMed1992

Protective effect of a T-cell-dependent immunosuppressive, B-cell-mitogenic protein (F3'EP-Si, or P90) produced by Streptococcus intermedius.

The role of a previously described bacterial protein (F3'EP-Si), now designated P90, in the survival of Streptococcus intermedius in the host was investigated, and the immunosuppressive and B-cell-mitogenic effects of this protein were further characterized. C57BL6 mice treated with P90 were about 50 times more susceptible to infection with this bacterium than untreated mice. One of seven splenocytes of C57BL/6 mice were activated by P90. Marked splenomegaly was observed in mice treated with P90, with increased numbers of splenic mononuclear cells and polyclonal immunoglobulin-secreting plaque-forming cells. Peak responses were seen on day 3 for immunoglobulin M (IgM) and on day 5 for IgG, with an isotypic pattern consisting predominantly of IgG2a and IgG2b. When mice were treated with P90 before being primed with sheep erythrocytes, polyclonal immunoglobulin synthesis was accompanied by an ephemeral stimulation of the specific immune response against sheep erythrocytes that was quickly replaced by a dramatic immunosuppression. In contrast, when mice were treated with P90 after being primed, the polyclonal activation was comparatively much less evident and there was no suppression of the specific immune response. Immunosuppression was considerably reduced in mice thymectomized as adults or depleted of CD8+ cells. Adoptive transfer experiments showed that B cells obtained from P90-treated mice were less able to respond to an antigenic challenge, even in the presence of normal T cells, and that T cells obtained from P90-treated mice could actively suppress the specific immune response of normal B cells.

Animals↗
PubMed1991

Extrathymic origin of intestinal intraepithelial lymphocytes bearing T-cell antigen receptor gamma delta.

The kinetics of postnatal intestinal colonization by T cells carrying gamma delta and alpha beta T-cell antigen receptors were studied in nude and normal mice by flow cytometry and immunohistology. Furthermore, gamma delta and alpha beta T-cell development was analyzed in lethally irradiated mice that were reconstituted by fetal liver precursors with or without a thymus. Our results establish that a major subpopulation of gamma delta intestinal intraepithelial lymphocytes is produced from uncommitted precursors at extrathymic sites. This work further shows that a small pool of T cells carrying alpha beta T-cell receptors can also differentiate extrathymically from CD3- fetal liver precursors but with rates of production and peripheral expansion much reduced as compared with those observed in thymus-bearing animals.

Animals↗
PubMed1991

Effector T lymphocytes present in demyelinating lesions induced by Theiler's virus.

Theiler's virus causes chronic primary demyelination associated with viral persistence in SJL/J mice. We have investigated the effector functions of T lymphocytes isolated from inflammatory brain lesions to detect a local immune dysfunction associated with viral persistence. In vitro, CD4+ T cells induced B-lymphocyte proliferation and antibody secretion; CD8+ T cells had cytolytic activity. Therefore, Theiler's virus persistence does not include local immune unresponsiveness.

Animals↗
PubMed1991

Clonal analysis of B lymphocyte responses to Plasmodium chabaudi infection of normal and immunoprotected mice.

Parasite infection causes marked perturbations in the host immune system, as shown by hypergammaglobulinemia, autoimmunity and immune depression, but there is little information on the number, specificities and performance of B cell clones activated in the course of infection. We have addressed these questions in a model of murine malaria induced by Plasmodium chabaudi, where primary infection results in very marked B cell responses that shift in Ig isotype pattern in immunoprotected animals, and where immunity can be transferred to naive recipients by injection of serum from late, but not early, infection. We have quantitated B cells responding to infection in two distinct functional compartments, namely blast cells and Ig-secreting cells, and compared normal with immune animals. We have also determined the frequencies of clonal specificities towards several autoantigens (DNA, myosin, transferrin and red cells), non-self protein or polysaccharide antigens (KLH, levan and dextran), and parasite antigens in both compartments, by measuring blast cell reactivities in limiting dilution analyses and Ig secretion in ELISASPOT assays. This experimental design allowed us to assess the specificity of the B cell responses, to compare the clonal composition of these two B cell compartments, and to evaluate putative specific response regulation at the step of terminal differentiation. Our results show that, in this particular experimental system: (i) B cell responses in primary infection are truly non-specific while immune animals show a greater ability to control the massive non-specific response; (ii) parasite specific B cells, particularly those committed to IgG production, are selectively stimulated in immune individuals; (iii) autoreactive B cells are not selectively stimulated, but increased autoantibody production may result from perturbation in the control of terminal differentiation in the respective clones; (iv) clones with specificity to some non-self antigens (e.g. KLH and dextran) are selectively engaged and regulated, which might have implications for the immunosuppression following infection.

Animals↗
PubMed1991

Proliferative T cell anergy to MIs-1a does not correlate with in vivo tolerance.

Intravenous or intraperitoneal priming of MIs-1b mice with cells from MIs-1a donors drastically reduces secondary in vitro proliferative responses to specific stimulation. We show here that: (i) priming leads to blast transformation of essentially all CD4+ T cells bearing V beta 6 receptors in spleen and lymph nodes, and to their marked clonal expansion; (ii) secondary in vivo (or in vitro) challenges have no effect on the state of activation and numbers of V beta 6 CD4 T cells, which, however, migrate to the site of antigenic exposure; (iii) priming results in the differentiation of specific V beta 6 CD4 T cells to effector helper activities, manifested in vivo by marked increases in the numbers of splenic plasma cells, which include terminally differentiated donor MIs-1a B cells; (iv) primed mice show accelerated 'second set' rejection of antigenic cells; and (v) MIs-1b mice, thymectomized as adults before exposure to MIs-1a cells, show immune responses that are equivalent to those of control animals. We conclude that, in this experimental system, proliferative 'anergy' does not correlate with tolerance but with memory, and relates to the determination of class in immune responses.

Animals↗
PubMed1990

V beta 17 gene polymorphism in wild-derived mouse strains: two amino acid substitutions in the V beta 17 region greatly alter T cell receptor specificity.

Of 41 wild-derived mouse strains analyzed, 14 contained T cells bearing V beta 17 receptors in spite of the concomitant expression of I-E antigens. Reciprocal F1 and F2 hybrids of one of these strains, PWK, with laboratory strains revealed different patterns of V beta 17 T cell deletions from those observed with V beta 17 T cells from SJL, implying that the two V beta 17 regions are associated with recognition of distinct superantigens. The structures of the V beta 17 alleles differ by two amino acid substitutions, which lie together in an area distant from the predicted site of T cell receptor interaction with peptide-MHC complexes but overlapping with that implicated in V beta 8.2 recognition of Mls-1 superantigen. This demonstrates that the self-superantigen leading to V beta 17 T cell deletion varies with the allele of the receptor gene and confirms that T cell deletions by such ligands involve interactions with a region of the V beta domain that is distinct from the conventional combining site.

Amino Acid Sequence↗
PubMed1990

Localization of gamma/delta T cells to the intestinal epithelium is independent of normal microbial colonization.

Using monoclonal antibodies identifying all gamma/delta and alpha/beta T cell receptors in cytofluorometric analysis, we have compared the composition of intestinal intraepithelial lymphocytes (i-IEL) in euthymic and athymic germ-free (GF) and conventional (SPF) mice. The results show a marked influence of microbial colonization in the numbers of single-positive (CD4+ or CD8+) alpha/beta i-IEL, but little effect in the pool size or characteristics of gamma/delta i-IEL. In young athymic mice, virtually no alpha/beta i-IEL are detected, while considerable numbers of gamma/delta i-IEL remain, though reduced in GF animals.

Animals↗
PubMed1990

Thymic epithelium tolerizes for histocompatibility antigens.

The role of thymic epithelium in the establishment of tissue tolerance was analyzed with a murine chimeric system. All T cells differentiated from birth onward in a thymus comprising allogeneic epithelium and syngeneic hematopoietic cells. Embryonic thymic rudiments that contained no hematopoietic cells from C3H (H-2k) donors were grafted to newborn athymic (nude) BALB/c (H-2d) mice. Chimeras that had normal T cell numbers and function rejected third-party skin grafts, but permanently accepted grafts syngeneic to the thymic epithelium. In vitro functional assays did not always correlate with the state of tolerance in vivo. Thus, pure thymic epithelium induces tolerance to histocompatibility antigens.

Animals↗
PubMed1989

Characterization of B lymphocytes present in the demyelinating lesions induced by Theiler's virus.

Theiler's virus, a murine picornavirus, persists in the central nervous system of SJL/J mice and causes inflammation and demyelination in the white matter of spinal cord. We isolated inflammatory cells from the central nervous system of infected animals and studied their functions in vitro. Flow microfluorimetry analysis showed the presence of all major lymphocyte subsets, namely CD4+ and CD8+ T cells as well as B lymphocytes. B lymphocytes were activated in vitro and the antigenic specificity of secreted Ig was determined by immunoblotting. Secreted Ig reacted strongly with viral capsid proteins VP1 and VP2 and had neutralizing activity. They reacted also with two nonviral white matter components which were present only in infected animals. Therefore, it is likely that Igs secreted at the site of infection play a role in limiting virus spread. It is also possible that virus induced autoreactive antibodies participate in demyelination.

Animals↗
PubMed1989

Interleukin 2 receptor expression and interleukin 2 production in exponentially growing T cells: major differences between in vivo and in vitro proliferating T lymphocytes.

In the present study we have assessed the growth requirements for in vivo proliferating mature T cells. For that purpose we have selected experimental approaches which allow the study of exponential growth in vivo of a major fraction of T cells, and make it possible to obtain large numbers of T cells in cycle. Two types of growing T cell populations were used: peripheral T lymphocytes, proliferating exponentially after transfer into syngeneic athymic nude mice, and activated T cells in lymph nodes of normal mice draining the site of oxazolone administration. The results obtained show that mature T cell growth in vivo is not accompanied by expression of high-affinity interleukin 2 (IL2) receptor in the majority of activated cells, is not abrogated by in vivo administration of anti-IL2 receptor antibodies or enhanced by the in vivo injection of recombinant IL2, and that in vivo growing T cells do not produce detectable amounts of IL2, as evaluated functionally by limiting dilution assays or the presence of IL2 mRNA, detected by Northern blots or in situ hybridization. The presented data thus indicate that the rules known to apply to T cell activation and proliferation in vitro differ from those used by in vivo growing T lymphocytes, at least in the two systems studied.

Animals↗
PubMed1989

Different large deletions of T cell receptor V beta genes in natural populations of mice.

A panel of geographically separate Mus m. domesticus and Swiss mice from several sources was screened for deletions in the T cell receptor variable (V) beta locus. Four out of forty-three strains tested show a deletion identical to or larger than the deletion previously described in SJL mice. To our knowledge, this is the first time that such important V beta deletions are described in inbred or partially inbred wild-derived strains of mice. On the other hand there seems to be very little polymorphism between the remaining V beta genes. Expression of V beta genes in peripheral and intra-thymic T cells was tested using antibodies specific for different V beta polypeptide chains. Flow cytometry analysis revealed a high expression of V beta 6 and V beta 17 genes in the Copacabana Swiss-derived strain and an absence of V beta 17 expression in the WLA wild-derived strain. The three Mus m. domesticus strains (WLA, DDO and WBG) having deleted two to three additional V beta subfamilies compared to SJL present no apparent immune deficiencies or autoimmune disorders. We conclude that relatively few V beta genes may suffice for unimpaired survival of wild mice and that there is a selective pressure for the structural conservation of the remaining V beta genes.

Animals↗
PubMed1989

Transplantation tolerance correlates with high levels of T- and B-lymphocyte activity.

Mice tolerized (treated to make them tolerant) at birth to transplantation antigens by injection of semiallogeneic cells contain very high numbers of activated T and B lymphocytes in their spleen. Lymphoid hyperactivity correlates with the tolerant state: it is present only in animals accepting skin allografts. Tolerized mice that reject the allogeneic skin graft have approximately the same numbers of total and activated lymphocytes as normal mice. The high level of lymphocyte activation in tolerant mice persists for up to 1 year of age, although it declines with age, and is markedly increased by a secondary allograft. The magnitudes of both primary and secondary tolerant responses are significantly higher than the immunological response of a normal mouse rejecting the same type of allograft. These observations contradict concepts of clonal deletion or anergy as the basis of neonatally induced transplantation tolerance and may contribute additional approaches to experimentation and control of transplantation reactions.

Animals↗
PubMed1989

Preferential expansion of Ly-1 B and CD4- CD8- T cells in the polyclonal lymphocyte responses to murine T. cruzi infection.

Acute murine infection with T. cruzi results in polyclonal lymphocyte responses manifested by blast transformation of a large fraction of B, CD4+, and CD8+ cells. We describe here the finding of significant increases in the splenic representation of minor populations, Ly-1 + B cells and CD4-CD8- T cells. These lymphocyte populations might play an important role in the host response, as shown by T. cruzi infection of hosts that had been lethally irradiated and reconstituted with autologous bone marrow. Under these conditions, the splenic polyclonal PFC responses are nearly abrogated, and not restored by the transfer of syngeneic peritoneal cells which, however, reconstitute T15 idiotype production in the same hosts. Control levels of PFC responses, however, are reconstituted by transfer of syngeneic splenic T cells. Since bone marrow-reconstituted animals contain normal numbers of CD4+ and CD8+ T cells which are actually activated by infection, these results suggest the participation of other T cell populations in the host response to infection, as also suggested by the marked increases in T cell receptor gamma and delta messages detected in the spleen of infected animals. The implications of these findings in immunopathology of Chagas' disease are discussed.

Animals↗
PubMed1989

A model system for the analysis of B-cell activation and effector T-cell functions. T cell-dependent B-cell responses facilitated by anti-I-A antibodies.

We have attempted to develop an in vitro system where polyclonal B lymphocyte responses could be induced in 'antigen-like' conditions, that is, where surface immunoglobulin-dependent binding mediates interaction with a mitogen. Monoclonal anti-mu and anti-delta antibodies were covalently bound to lipopolysaccharide (LPS) and these complexes were shown to display mitogenic activity. Polyclonal plaque-forming cell (PFC) responses, however, were diminished in cultures stimulated by anti-mu-LPS (but not by anti-delta-LPS) indicating that 'anti-mu inhibition' of terminal B-cell differentiation also applies to 'specific' antibody responses. Moreover, the analysis of the functional activity of monoclonal antibodies to major histocompatibility complex (MHC) class II molecules revealed a surprising synergy between low, non-stimulatory concentrations of anti-mu-LPS (but not anti-delta-LPS) with anti-I-A antibodies. These responses are T-cell dependent and synergy with anti-mu-LPS conjugates can also be obtained with 'naturally' activated CD4+ cells isolated from normal donors. A model of molecular and cellular interactions was derived, which accounts for the present findings and is applicable in antigen-dependent lymphocyte collaboration.

Adjuvants, Immunologic↗