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H Y Tse

Publications and source records attributed to H Y Tse.

At least 37 records · Page 2Linked to original sources
PubMed1992

A combination of adoptive transfer and antigenic challenge induces consistent murine experimental autoimmune encephalomyelitis in C57BL/6 mice and other reputed resistant strains.

Adoptive EAE was induced in SJL mice by the transfer of MBP-primed and in vitro-stimulated donor lymph node cells into naive syngeneic recipients. Priming donor mice with OVA instead of restimulating MBP-primed donor cell with OVA resulted in no transfer of EAE. This apparent lack of disease, however, could be overcome if the recipients were subsequently challenged with MBP. When this transfer-challenge technique was applied to BALB/c and C57BL/6 mice, these reputed (MBP)EAE-resistant strains developed consistent and severe disease similar to that seen in susceptible strains. In fact, a survey of eleven (MBP)EAE-resistant strains, defined on the basis of their inability to mount an encephalitogenic response in recipient mice following the transfer of MBP-primed and in vitro activated lymph node cells, revealed that EAE could be induced in all these strains. Since the surveyed strains represented a wide spectrum of genetic backgrounds as well as the common MHC congenic haplotypes (H-2b,d,k,m,r,s,v), it is concluded that the machinery for recognition of MBP, i.e. MHC genes and the appropriate T cell receptors, is functionally intact in these resistant mice. While MHC and T cell receptor genes are required for T cell responses, they are not the limiting factors that confer resistance in murine EAE.

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PubMed1989

Parasite exposure elicits a preferential T-cell response involved in protective immunity against Eimeria species in chickens primed by an internal-image anti-idiotypic antibody.

Polyclonal anti-idiotype 1073 (anti-Id 1073), raised against a monoclonal antibody specific for the protective epitope(s) of Eimeria tenella sporozoites, induced cell-mediated immune (CMI) responses in bursectomized chickens. Whereas alhydrogel-adsorbed anti-Id 1073 was sufficient to engender the CMI response at 4 h after injection, induction of the CMI response at 24 h required both alhydrogel and muramyl dipeptide sterol. Exposure of immunized chickens to live parasites prompted a dichotomous effect on the CMI response engendered by anti-Id in that the 4-h CMI response was preferentially stimulated and the 24-h CMI response was down regulated. Both types of CMI response were transferable to naive chickens by T cells from anti-Id 1073 immune donors or by parasite-specific T cells from clones 21 and 27. These T-cell clones were generated from chickens immunized by repeated infections with E. tenella and showed in vitro proliferative responses to anti-Id 1073. The abilities of T cells from clone 21 to selectively transfer the 4-h CMI response and to generate gamma interferon to activate macrophages for their cytotoxic effects on Eimeria sporozoites correlate with the preferential stimulation by parasites of the 4-h CMI response in chickens immunized with anti-Id 1073. These data show that anti-Id 1073 mimics the protective epitope(s) of the parasite and primes chickens for protective CMI responses. Cytotoxic T cells, equivalent to the mammalian T-cell subset of the Lyt2+ phenotype, appear to be the primary effector T cells in the CMI response engendered by anti-Id 1073 against Eimeria parasites.

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PubMed1988

Influence of major histocompatibility complex H-2LD class I molecules on spleen colony-forming units.

To test whether the major histocompatibility complex class I genes are involved in the regulation of hemopoiesis, the stem cell activities of BALB/c-H-2dm2 (Dm2) mice, which are defective in the expression of H-2L antigens, have been compared with those of the wild-type, BALB/c-Kh, in in vivo and in vitro stem cell assays. In spleen colony-forming unit assays, Dm2 as hosts consistently supported a smaller number of colonies than did BALB/c-Kh. However, both Dm2 and BALB/c-Kh supported a comparable number of colonies in in vitro granulocyte-macrophage colony-forming unit and erythroid colony-forming unit assays. These observations together suggest that the mutation in Dm2 has not affected the hemopoietic potential of the stem cells but may probably affect the hemopoietic microenvironment for the development of the stem cells.

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PubMed1987

Insights into immune-response gene function using an Ia mutant mouse strain.

The class II genes of the major histocompatibility complex (MHC) encode the immune response-associated or Ia antigens. These highly polymorphic glycoprotein heterodimers have been shown to play a pivotal role in diverse immunological functions. Although the precise molecular and cellular interactions have yet to be elucidated, structural determinations on Ia molecules are known to control the immune response to foreign antigens. Several recent advances into our understanding of how Ia molecules function were made possible by the discovery of the B6,C-H-2bm12 (bm12) mouse strain. The bm12 strain carries a mutation that occurred spontaneously in one of its genes encoding an Ia polypeptide chain. Information from studies using bm12 include (1) insights into the evolution of class II genes and its functional significance; (2) the definition of multiple functional sites on Ia and their relative importance; and (3) the demonstration that Ia conformation is important in determining its functional capacity. These findings using the bm12 mutant are reviewed in the context of other recent studies of Ia recognition.

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PubMed1986

Chicken T lymphocyte clones with specificity for Eimeria tenella. I. Generation and functional characterization.

T lymphocyte clones reacting specifically with the antigenic components of Eimeria tenella were generated from splenic lymphocytes of immunized chickens and were maintained for 12 to 14 wk in vitro. These T cell growth factor-dependent T lymphocyte clones from bursectomized and normal chickens proliferated in vitro when stimulated with antigens from different developmental stages of homologous but not heterologous species of the parasite. Specific proliferative responses of the cloned T cells showed an absolute requirement for antigen presentation by histocompatible antigen-presenting cells. Some of the T cell clones exhibited functionally discrete interactions with syngeneic primed B cells; 25% of the T cell clones from immunized normal chickens and 7% of those obtained from immunized bursectomized chickens showed antigen-dependent helper activity and induced specific antibody production by syngeneic primed B cells. Of the T cell clones from immunized normal chickens, 19% showed suppression of in vitro antibody production in comparison to 7% of those isolated from immunized bursectomized chickens. The frequency of cloned T cells with ability to induce cytotoxic activity in macrophages against the sporozoites of E. tenella was much higher in those isolated from bursectomized chickens (80%) than in those isolated from normal chickens. Because both bursectomized and normal chickens can be immunized by repeated infections, differences in the distribution among cloned T cells suggest different effector mechanisms of immunity against coccidiosis in these chickens. Lack of B cells seem to affect the development of T cell immunity as reflected by slower development of immunity and enhanced activation of cytotoxic T cell function.

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PubMed1985

Characterization of a dominant anti-Ia idiotype using the IA mutant mouse strain B6.C-H-2bm12.

Initial studies of antibody recognition of Ia molecules using the IA mutant mouse strain bm12 suggested that two anti-Ia monoclonal antibodies (mAbs), 25-9-17 and 34-5-3, share several features: (1) indistinguishable serologic specificity including a lack of reactivity with Iabm12, (2) binding of the same spatial epitope (cluster), and (3) definition of a cross-reactive idiotype (CRI) as defined by xenogeneic antisera. In the present study we characterize a rabbit anti-idiotype (anti-Id) to 25-9-17 by affinity chromatography, and demonstrate that it detects at least two distinct idiotopes, one shared by 25-9-17 and 34-5-3 designated CRI (25-9-17) and one unique for 25-9-17 molecules. Experiments were also undertaken to determine whether CRI (25-9-17) represents a measurable component of allogeneic humoral responses to Iab antigens. By both absorption analyses of a polyspecific antiserum and production of antigenically-restricted antisera using bm12 mice, CRI (25-9-17) was found to represent a significant proportion of the antibodies to Iab. By several criteria it was shown that the CRI (25-9-17)+ molecules were among the antibodies defining the serologic lesion of bm12 mice. In preparation for future studies to alter in vivo T-cell responses involving recognition of Ia (e.g. graft vs host disease and allogeneic transplant rejection), various immunization protocols and mouse strains were tested for induction of Id (25-9-17) following in vivo administration of various anti-idiotypic reagents. Rabbit anti-Id (25-9-17) successfully induced CRI (25-9-17) positive molecules in all strains tested regardless of IA or Ig genotype. Moreover, some of these treated mice produced antibodies to an Ia determinant missing on bm12 cells, suggesting that they recognize the same serologic determinant as mAb 25-9-17.

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PubMed1985

The murine bm12 gene conversion provides evidence that T cells recognize predominantly Ia conformation.

The structure of the highly polymorphic Ia dimer is the genetically determined factor that controls the immune response to foreign antigens, albeit the mechanism remains unresolved. However, it is clear that, in diverse immune responses, effector T lymphocytes require recognition of self-Ia and foreign antigenic determinants on the surface of an antigen-presenting cell or an antibody-secreting B cell. Furthermore, a single Ia molecule has been found to possess several independently acting functional domains. In this report T-cell recognition of Ia was limited to a single, defined structure by using the Ia mutant mouse strain B6.C-H-2bm12 (bm12). The Ia determinant being recognized is the site of the mutation that represents a difference in three of five amino acid residues in a hypervariable region of its beta chain. This mutation has been proposed to have resulted from a gene conversion-like event and is known to have functional importance. Recognition of the bm12 mutation site was studied here in in vitro cultures of T cells generated against Iabm12 antigens. The specificity of these alloreactive T cells was tested by using stimulator cells expressing various Ia alloantigens of known structure. Our findings provide direct genetic evidence that T cells recognize predominantly conformational determinants on Ia molecules and not their primary structure. The implications of these findings on our understanding of the genetic control of the immune response and the potential to modulate these responses in an antigen-specific way are discussed.

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PubMed1984

Delineation of Ia:nominal antigen complementary determinants recognized by T cells in studies of gene complementation in response to insulin.

The immune response to beef insulin in mice is controlled by genes in the IA subregion. We have previously shown that B6.C-H-2bm12 (bm12) mice, an A beta gene mutation of B6, have a selective loss of responsiveness to beef insulin, whereas other IAb controlled responses such as (TG)AL and collagen are unchanged. F1 hybrid mice between two nonresponder genotypes Ik and Ibm12 were found to be good responders to beef insulin suggesting functional complementation. In this report, we define the cellular and molecular basis of this complementation by investigating the determinants on Ia molecules and nominal antigen that are recognized by (B10.A X bm12)F1 proliferating T cells. Genetic analyses demonstrated that the Ik region was the only nonresponder genotype that complemented Ibm12, thus restoring responsiveness to beef insulin. More precisely an IAk and not an IEk gene product was found to be responsible for this complementation. Antibody blocking studies furthermore showed that the A alpha b:A beta k hybrid Ia mediated the response to beef insulin in (B10.A X bm12)F1 mice. Clonal analyses of the response to beef insulin in these F1 mice confirmed these conclusions, because the insulin-specific response in all 21 F1-T cell clones studied thus far was found to be dependent upon presentation via the A alpha b:A beta k hybrid Ia molecule. Dissection of the antigenic specificity of the F1-T cell clones demonstrated recognition of at least two insulin determinants, one A-loop (A8-A10) associated and the other non-loop (A4 or B chain) associated. Therefore these studies identify the molecular and antigenic basis of the Ir gene complementation seen in the response to beef insulin of (B10.A X bm12)F1 hybrids.

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PubMed1984

T lymphocyte-dependent B lymphocyte proliferative response to antigen. II. Induction of polyclonal B lymphocyte activation of normal B cells and of Lyb-5- B cells from xid mice via recognition of self-IA antigens.

We extended our investigations into the genetic requirements and antigen dependence for the induction of polyclonal B lymphocyte proliferation by primed T lymphocytes. By using recombinant inbred mouse strains and antigen-specific T lymphocyte clones that lack alloreactivity, the genetic requirement was mapped to the IA subregion of the MHC. Furthermore, approaches that prevented or limited the accessibility of antigens to the B lymphocyte surface demonstrated that antigen binding onto the B lymphocyte surface was probably not necessary for induction of B lymphocyte proliferation. These experiments suggest strongly that T lymphocyte recognition of B lymphocyte Ia molecules in the absence of sIg cross-linking or in the absence of antigen bound nonspecifically to B lymphocytes can cause cellular activation. Similar T lymphocyte-dependent B lymphocyte activation was seen when Lyb-5- cells from CBA/N mice with the xid defect were cultured. Increases in the number of cells secreting immunoglobulins could be detected in the proliferating B lymphocyte cultures, suggesting that the culture conditions had fulfilled the requirements for B lymphocyte differentiation into antibody-producing cells. Although anti-Ig did not interfere with the B lymphocyte proliferative responses, it did diminish the number of cells secreting immunoglobulins. The implications of these experiments in extending our understanding of the activation pathway of Lyb-5- and Lyb-5+ B lymphocytes are discussed.

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PubMed1984

Assessment of antigen-specific restriction sites on Ia molecules as defined by the bm12 mutation.

To further delineate the functional defects of bm12 mice in antigen presentation, we analyzed antigen-specific T lymphocyte clones derived from B6 or bm12 for their ability to recognize antigens presented on either B6 or bm12 APC. Both complex antigens, such as PPD and GAT, and restricted antigens, such as beef insulin, were used. Our results indicate that for complex antigens, more than 50% of the B6 T lymphocyte clones recognized antigens only if presented by B6 APC, whereas the rest could not discriminate B6 from bm12 APC. Similarly, bm12 T lymphocyte clones responding to complex antigens could be divided into two groups depending on the sources of the APC. We have also isolated B6 T lymphocyte clones specific for the more restricted antigen, beef insulin, to which bm12 failed to respond. All B6 T lymphocyte clones could be stimulated only with B6 APC and not with bm12 APC. These data are consistent with the notion that there are antigen-specific association sites on the Ia molecule, and that complex antigens have more than one such association site. Furthermore, these studies demonstrate that both the gain and loss determinants associated with the bm12 mutation are recognized by a significant number of bm12 and B6 antigen-specific T lymphocyte clones, respectively, thus defining the importance of this region of the A beta polypeptide chain in antigen presentation.

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PubMed1982

B lymphocyte immune response gene phenotype is genetically determined.

We examined the effects of the developmental milieu on the capacity of B cells to undergo immune response gene-controlled, T cell-dependent polyclonal proliferation. Although I-Aq poly(Glu60 Ala30 Tyr10)n (GAT)-nonresponder T cells developing in a responder environment become phenotypic GAT-responders, I-Aq B cells remain unresponsive to GAT, even after maturation in a GAT-responder animal. Conversely, (B10.A x B10.Q)F1 ([GAT responder x GAT nonresponder]F1) T cells developing in a B10.Q GAT nonresponder host fail to respond to GAT, but F1 B cells from the same F1 leads to parent chimeras make excellent proliferative responses in the presence of GAT and responder T cells. Thus, by this assay, B cell immune response gene function is genetically determined and is not affected by the developmental milieu.

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PubMed1981

T lymphocyte-dependent B lymphocyte proliferative response to antigen. I Genetic restriction of the stimulation of B lymphocyte proliferation.

For the purpose of examining more closely the interaction between T and B lymphocytes, we have developed an in vitro T lymphocyte-dependent B lymphocyte proliferation assay. Proliferation of B lymphocytes in response to antigen was found to depend on the presence of primed T lymphocytes; the B lymphocytes could be derived from nonprimed animals. It appears that these B cells were nonspecifically recruited to proliferate. This nonspecific recruitment, however, was found to be Ir-gene restricted in that B lymphocytes from B10.S mice, which are genetic nonresponders to the polymer Glu60-Ala30-Tyr10 (GAT), could not be stimulated by GAT-primed (responder X nonresponder) F1 T cells. The apparent lack of antigen specificity in the face of Ir gene-restricted T-B interaction may have important implications in our understanding of the recognition unit(s) on T lymphocytes.

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PubMed1981

Antigen-specific clones of proliferating T lymphocytes. I. Methodology, specificity, and MHC restriction.

In this report we describe in detail a new method for cloning antigen-specific, proliferating T lymphocytes directly from primed murine lymph nodes after 3 days of activation in vitro. After expansion in liquid culture the cells from the colonies were shown to be antigen specific and to require I-A histocompatible, irradiated spleen cells for stimulation. For hapten-carrier-type antigens, the T cells were shown to be carrier specific in their recognition but they were also capable of distinguishing the presence of the hapten. Recloning of small numbers of these cells in soft agar under conditions of high plating efficiency yielded true clones (i.e., populations derived from a single cell) whose antigen specificity was identical to that of cells from the original colony. The fact that a clone of T cells was I-A restricted in its antigen recognition demonstrates that suppressor T cell function cannot account for the phenomenon of major histocompatibility complex restriction.

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PubMed1980

Direct cloning and extended culture of antigen-specific MHC-restricted, proliferating T lymphocytes.

The development of antigen-specific, T-cell lines has been a subject of intensive investigation by many laboratories interested in the problems of the nature of the T-cell receptor and the mechanism of major histocompatibility complex (MHC) restriction. We describe here a modification of the soft agar cloning technique which has allowed us to rapidly generate and expand proliferating T-lymphocyte clones directly from murine lymph nodes. Using this technique, we demonstrate that such T-cell clones are antigen specific and require I--A compatible antigen-presenting cells for stimulation.

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PubMed1980

Cell-cell interactions in the T cell proliferative response. I. Analysis of the cell types involved and evidence for nonspecific T cell recruitment.

In the antigen-induced T cell proliferative response, it has been firmly established that antigen-specific T cell activation signals are provided by a specialized antigen-presenting cell (APC). However, the number of responding T cell populations involved has not been clearly delineated. This problem can be analyzed by plotting the logarithm of the number of cultured cells against the logarithm of the response. This yields a straight line, the slope of which indicates the minimum number of interacting cell populations that are required to give the response. In the antigen-induced T cell proliferative response, this number is 3. Based on their ability to shift the slopes of the log cell number-log response line, two of the populations were identified to be T cells. The third cell, which was present in irradiated spleens, possessed certain properties of the APC. Of the two T cells, one was antigen-specific and the other could come from normal unprimed animals. The frequency of antigen-specific proliferating T cells in primed animals was estimated to be only 1 in 1.3 x 10(3), and a large proportion of the proliferation was shown to be due to unprimed cells. Furthermore, without the need to use antigen-pulsed macrophages, this slope analysis demonstrated convincingly that the successful interaction between APCs and proliferating T lymphocytes is determined by products of the I-region immune response genes.

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PubMed1978

Separation of helper and suppressor T lymphocytes. III. Positive and negative effects of mixed lymphocyte reaction-activated T cells.

Using a Ficoll velocity sedimentation gradient, we provide evidence to show that stimulatory and inhibitory activities induced in mixed lymphocyte culture belong to two distinct subpopulations of T cells. Slow- to medium-sedimenting, nonproliferating cells enhance the humoral response of normal cells to SRBC whereas fast-sedimenting cells inhibit that response. Cytotoxic lymphocytes are found in the same fractions as suppressor cells but appear to be differentiable from the latter in terms of maturation kinetics and specificity.

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