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F W Shen

Publications and source records attributed to F W Shen.

At least 73 records · Page 4Linked to original sources
PubMed1981

Lyb-2 system of mouse B cells. Evidence for a role in the generation of antibody-forming cells.

The Lyb-2 cell-surface alloantigens of the mouse are selectively and perhaps exclusively expressed in the B lymphocyte lineage, but not on antibody- forming cells. Thus if the Lyb-2 molecule is concerned in specific B cell function, it must participate in the generative phase of the antibody response. Accordingly, monoclonal Lyb-2 antibody was found to depress the plaque- forming cell (PFC) response to sheep erythrocytes in 5-d Mishell-Dutton assays when added within the first 3 d of culture, but not later. The rate of PFC generation was not affected, signifying an absolute reduction in the number of PFC generated. Because reduction of PFC counts by Lyb-2 antibody was not affected by exclusion of Lyt-2(+) T cells, it is unlikely that the reduction depends on augmented suppression by T cells. Augmented B cell- mediated suppression is also unlikely, because the PFC response of serial combinations of congenic Lyb-2.1 and Lyb-2.2 cells, in the presence of monoclonal Lyb-2.1 antibody, was reduced only in direct proportion to the number of Lyb-2.1 cells present. The PFC response of Lyb-2.1/Lyb-2.2 heterozygous cells was not reduced by Lyb-2.1 antibody, presumably because generation of PFC is impeded only if most Lyb-2 sites are blocked. Further evidence that the molecule identified by Lyb-2 plays a critical role in the generation of antibody-forming cells (AFC) in response to T-dependent antigen comes from the finding that Lyb-2 antibody does not reduce the PFC response to the T-independent antigens trinitrophenylated (TNP) Brucella abortus and TNP-FicolI, although elimination of Lyb-2(+) cells from the starting population by Lyb-2 antibody and complement reduces the PFC response to T- dependent and T-independent antigens alike.

Animals↗
PubMed1981

A pseudogene homologous to mouse transplantation antigens: transplantation antigens are encoded by eight exons that correlate with protein domains.

We have isolated about 30 to 40 different BALB/c mouse sperm DNA genomic clones that hybridize to cDNA clones encoding proteins homologous to transplantation antigens. One of these clones (27.1) was selected for sequence because it was polymorphic in Southern blot analysis of the DNAs from BALB/c and CBA mice. A fragment of 5.7 kilobases of this clone was completely sequenced and found to contain a pseudogene whose sequence is highly homologous to the sequences of known transplantation antigens. Pseudogene 27.1 is split into eight exons that correlate with the structurally defined protein domains of transplantation antigens. Using Southern blot hybridization on the DNAs of different inbred mouse strains, we mapped the pseudogene to the Qa-2,3 region, a part of the Tla complex on chromosome 17 that is adjacent to the major histocompatibility complex. The Qa2,3 region encodes lymphoid differentiation antigens homologous to the transplantation antigens in size, in peptide map profiles and in their association with beta2-microglobulin. These mapping studies suggest that gene 27.1 may be a pseudogene for eigher a Qa antigen or an as yet undefined transplantation antigen. Accordingly, we may have isolate genes encoding lymphoid differentiation antigens of the Tla complex as well as those encoding transplantation antigens among the 30 to 40 different genomic clones isolated from our sperm library.

Base Sequence↗
PubMed1980

Influence of Fv-1 alleles on cellular expression of gp70.

Type-variants of gp70 (glycoprotein-70), which is the major envelope protein of C-type mouse virus and is also found in plasma membranes, are identified immunogenetically by the antigens Gix and Ec. Cellular expression of Gix+ gp70 does not depend on production of virus, but expression of Ec+ gp70 (formerly X-gp70) has been observed only in AKR and other strains of mice that produce large amounts of virus throughout life. To test the inference that cellular expression of Ec+ gp70 is secondary to production of virus we examined the effect of Fv-1 alleles, which govern the replicability of N-tropic and B-tropic C-type virus, on the expression of Ec+ gp70 on thymocytes. By typing thymocytes of Fv-1-congenic mice for Ec+ gp70 was found that manifestation of the Ec+ gp70 phenotype requires the Fv-1n allele, which is permissive for replication of N-tropic virus produced by AKR and other virus-producing mouse strains. Substitution of the Fv-1b allele for the Fv-1n allele abolishes demonstrable expression of Ec+ gp70 by AKR thymocytes at ages up to 9 mo, the oldest AKR mice tested.

Animals↗
PubMed1980

Developmental and communicative interrelations of Ly123 and Ly1 cell sets.

To distinguish and define the differentiative and communicative relations of Ly123 and Ly1 cells in generating specific helper-effector (HE) (Ly1:HE) and specific suppression-inducing (SI) (Ly1:SI) cells, these two functional sets were generated from various combinations of congenic genetically marked sets of cortisone-resistant nylon-purified thymocytes (CRNPT) by culture on antigen-primed macrophages (M phi) (the (T-M phi culture system). It was thus shown that Ly1:HE and Ly1:SI cells are produced by differentiation from antecedent Ly123 cells. Ly1:HE and Ly1:SI are separate Ly1 populations; generationof Ly1:HE cells requires the presence of Ly1 cells, whereas the generation of Ly1:SI cells does not. Although the Ly23 CRNPT set, which is included when Ly123 cells are positively selected with Lty-2 antiserum is ruled out as a precursor source of Ly1:SI cells, the possibility of a communicative role for Ly23 cells in generating Ly1:SI cells remains to be investigated. The role of the Ly1 set required for the generation of Ly1:HE cells from CRNPT is communicative, not differential; and it is not a precursor source of Ly1:HE or Ly1:SI cells in the CRNPT population. It remains to be seen whether the use of additional phenotypic markers will distinguish subsets of Ly123 and Ly1 cells engaged in these several functions.

Animals↗
PubMed1980

Cell cooperation during in vivo anti-hapten antibody responses. V. Two synergistic Ly-1+23- helper T cells with distinctive specificities.

Experiments were carried out to determine the antigen specificity of two distinct helper T cells (Th) that act synergistically in adoptive secondary in vivo anti-hapten antibody responses. Both Th were present in anti-Ly-2 and-complement-treated spleen T cell populations, implying that both Th are Ly-1+,23-. Adding normal T cells or T cells primed to other carriers to specific carrier-primed T cells, using a variety of different protocols did not affect the helper activity of the specifically primed Th. Thus, both Th apparently are antigen-specific. Furthermore, Th primed with one carrier and boosted with that carrier plus hapten linked to a noncross-reactive carrier cannot help B cells. However, if a mixture of Ly-1 T cells from mice primed with two different carriers is transferred along with B cells, and the mice are boosted with hapten coupled to one of the two priming carriers, then giving the other carrier induces a significant increase in antibody production. Thus, only one of the two Th (Th1) requires a hapten-carrier bridge, while the other does not (Th2). However, both Th1 and Th2 are clearly antigen-specific and require stimulation with antigen to exert helper activity. Furthermore, these experiments strongly suggest that Th2 cannot express helper function in vivo in the absence of Th1. These findings, and the absence of Th2-like cells in agammaglobulinemic mice, were correlated with other studies in which two helper activities have been described. It was concluded that in vivo responses require an effective Th1-B cell interaction, whereas Th2, if stimulated with antigen, will augment certain portions of the antibody response, such as idiotype or allotype, and thus influence the quality of the antibody response directly.

Animals↗
PubMed1980

Ly-1 inducer and Ly-1,2 acceptor T cells in the feedback suppression circuit bear an I-J-subregion controlled determinant.

An I-J-subregion controlled determinant is expressed on Ly-1 inducer and Ly-1,2 acceptor T cells in the feedback suppression circuit. Ly-1 T cells absorb the I-J antibody reactive with the Ly-1,2 acceptor T cell, suggesting that both inducer and acceptor T cells have the same I-J determinant. Since less than 10 percent of Ly-1 or Ly-1,2 T cells are killed by anti-I-J plus complement treatment, the I-J determinant demarcates functionally distinct subsets of both the Ly-1 and Ly-1,2 T-cell sets. This I-J determinant is not expressed on a detectable number of Ly-1 helper T cells which induce B lymphocytes to produce anti-sheep red cell antibody in tissue culture.

Animals↗
PubMed1980

Lymphotoxin production by subsets of T cells.

Lymphotoxin is produced by T cells sensitized to antigen upon re-exposure in vitro. It is also elicited by mitogen treatment. Its production has been correlated with delayed-type hypersensitivity and it may be a mediator of that phenomenon. We have examined the Ly phenotype of the subset(s) of T cells that produce lymphotoxin in order to investigate the relationship of lymphotokin killing to allo-killing mediated by Ly2+ T cells. We have found that Ly1 T cells sensitized to ovalbumin secrete more lymphotoxin than Ly2 cells. The ovalbumin-sensitized T cells do not lyse their target in a short term 51Cr-release assay even when "glued" to the target with Con A. Thus, lymphotoxin-producing cells differ phenotypically from the previously defined cytotoxic T cells that bear the Ly2 differentiation marker.

Animals↗
PubMed1980

Antigen-antibody complexes generate Lyt 1 inducers of suppressor cells.

Pretreatment of H-2b mice with KCl-extracts of an H-2d tumor (L1210) together with L1210 antibody rendered the mice incapable of mounting an effective immune response to viable L1210 tumor cells. This specific immunosuppression was associated with inhibition of macrophage functions, which could be used to quantitate the level of suppression. Lyt 1 cells (but not Lyt 2 cells) from either the spleen or thymus of mice pretreated with antigen-antibody complexes could adoptively transfer the suppressed state to normal mice. The Lyt 1 cells that transferred the suppression were resistant to low (20 mg/kg) doses of cyclophosphamide (Cy) but required a Cy-sensitive precursor and/or amplifier cell to be activated. Once activated, they required a Cy-sensitive Lyt 1 2 3 acceptor cell in the normal recipient to effectively suppress the adoptive host's macrophages. Our results indicative that immune complexes in concert with a Cy-sensitive T cell generate Cy-resistant Lyt 1 inducers of suppression. These in turn activate normal thymic or peripheral Lyt 1 2 3 acceptor cells, resulting in the generation of effector suppressor T cells. These suppressor cells are most likely the proximate cause of the inhibition of macrophages we have observed in vivo.

Animals↗
PubMed1980

Feedback suppression: phenotypes of T cell subsets involved in the Ly1 T cell-induced immunoregulatory circuit.

Ly1 inducer t cells (Ly1:SI) activate resting T cells to generate potent suppressor activity. Primed Ly1:SI generated in vitro were assayed for suppression induction in cultures containing B cells and various Lyt T cell sets that had been positively and/or negatively selected using alpha Lyt sera. These experiments both reaffirm the previously reported requirement for an Ly123 T cell in suppression by Ly1:SI and implicate a third T cell subset, which is absolutely required for the full expression of Ly1:SI-induced feedback suppression. This subset of T cells has the cell surface phenotype, Ly1- Ly23+ 1J+ Qa-1-.

Animals↗
PubMed1979

Inhibition of H-Y cell-mediated cytolysis by H-2Db antiserum.

Assays of H-Y-specific cell-mediated cytolysis (CMC) in vitro were carried out with B6 female effector cells and B6 male target cells. This lytic system depends on compatibility for H-2Db but not for H-2Kb. Antibody to H-2Db but not to H-2Kb blocked the CMC assay. However, maximal blocking required exposure to the target cells to H-2Db antibody for up to 2 h. This interval is far longer than would be required for blocking of a pre-existing H-Y:H-2Db complex, and seems more consonant with a membrane reorganization bringing H-Y and H-2Db together, as proposed from mapping studies. The question whether the postulated configurational change affecting H-Y and H-2Db is a necessary feature of CMC awaits further study.

Animals↗
PubMed1979

Genetic control of immunoregulatory circuits. Genes linked to the Ig locus govern communication between regulatory T-cell sets.

Antigen-stimulated Ly1:Qa1+ cells induce a nonimmune set of T-acceptor cells (surface phenotype Ly123+Qa1+) to participate in the generation of specific suppressive activity. The experiments reported here were designed to test the possibility that the interaction between T-inducer and T-acceptor cells might be governed by genes linked to the Ig locus. We find that inducer:acceptor interactions occur only if the inducer and acceptor T-cell sets are obtained from donor that are identical at the Ig locus and are independent of the Ig locus expressed on the B cells used for assay of T-helper activity. In addition, experiments using inducer and acceptor T cells from the congenic recombinant BAB. 14 strain show that T-T interactions are not governed by Ig-CH genes, per se. These data indicate that T-inducer: T-acceptor interactions are governed by Ig-linked genes that may control expression of VH-like structures on T cells, or control expression of as yet unidentified cell-surface molecules.

Animals↗
PubMed1979

Direct evidence that natural killer cells in nonimmune spleen cell populations prevent tumor growth in vivo.

Relatively large numbers of nonimmune spleen cells do not protect against the local growth of two lymphomas. However, this heterogeneous population of splenic lymphocytes contains a subset of cells that efficiently protects against in vivo tumor growth. This cell population (cell-surface phenotype Thyl.2(-)Ig(-)Ly5.1(+)) represents less than 5 percent of the spleen cell population and is responsible for in vitro NK-mediated lysis. Although these studies clearly and directly demonstrate that Ly5(+) NK cells selected from a heterogeneous lymphoid population from nonimmune mice can protect syngeneic mice against local in vivo growth of two different types of tumor cells (in contrast to other lymphocyte sets within the spleen), they do not directly bear upon the role of NK cells in immunosurveillance. They do indicate that highly enriched Ig(-)Thyl(-)Ly5(+) cells, which account for virtually all in vitro NK activity, can retard tumor growth in vivo. It is difficult to ascribe all anti-tumor surveillance activity to NK cells, because they probably do not recirculate freely throughout the various organ systems of the body. Perhaps NK ceils may play a role in prevention of neoplastic growth within discrete anatomic compartments where there is rapid differentiation of stem cells to mature progeny (e.g., bone marrow, spleen, and portions of the gastrointestinal tract)and may normally act to regulate the growth and differentiation of non-neoplastic stem cells. Long-term observation of chimeric mice repopulated with bone marrow from congenic or mutant donors expressing very low or very high NK activity may help to answer these questions.

Animals↗
PubMed1979

Idiotypic determinants on T-cell subpopulations.

Killer T cells with specificity for major histocompatibility antigens have been shown in mice and rats to display idiotypic receptors allowing the lysis of such cells at the effector phase by anti-idiotypic antibodies and complement. A comparison was made between idiotypes displayed by Lyt-1-2+3+ and Lyt-1+2-3- T blasts, generated in the same mixed leucocyte culture (MLC), across an entire H-2 locus barrier. This was done by absorption of anti-idiotypic antibodies with respective T blasts, followed by estimation of the ability of the absorbed antiserum to inhibit MLC or killer T-cell function. Further, the capacity of Lyt-purified, MLC-generated T blasts to provoke specific unresponsiveness via anti-idiotypic immunity in syngeneic recipients was analyzed. Taken together, the results demonstrate that Lyt-1+2-3- T blasts responsible for the major part of MLC proliferation have distincly different idiotypes from those on the Lyt 1-2+3+ killer T cells. That the idiotypes on the killer T-cell presursors can serve as triggering sites for induction of effector T-cell function was then suggested by experiments with Lyt-1-2+3+-purified, normal T cells as precursor cells in vitro. The fact that autoanti-idiotypic antibodies may circumvent the need for helper Lyt-1+2-3- T cells in the generation of allospecific killer T cells indicates that the former cells may normally function partly via such anti-idiotypic reactions.

Animals↗
PubMed1979

Antigen-binding T cells: dose response and kinetic studies on the development of different subsets.

We have described a number of the parameters involved in the in vitro induction of specific SRBC-binding T cells (T rosette-forming cells, T-RFC). Although T-RFC precursors pass through nylon, most of the induced cells do not; nor do detectable numbers of Ly 1+2, 3- cells bind antigen with sufficient stability to form rosettes. The ratio of Ly 2,3:Ly 1,2,3 T-RFC varies with time after immunization and with the dose of antigen used for stimulation. Relatively high or low doses of antigen selectively induce Ly 1,2,3 T-RFC. Ly 2,3 T-RFC, when they appear, follow Ly 1,2,3 T-RFC. Pretreatment of T cells with anti-Ly sera before RFC induction prevents formation by Ly2+ T-RFC. Since anti-Ly 1 treatment blocks RFC formation and since Ly 1,2,3, T-RFC always precede the appearance of Ly 2,3, T-RFC, our results suggest that some Ly 1+ cells (Ly 123 at least, but perhaps also Ly 1) may act as inducers, precursors, and/or amplifiers for Ly 2,3 RFC as they appear to do for Ly 2,3 suppressor and killer cells. Thus, our results confirm and extend the observed similarities between T-RFC and other Ly 2+ cells such as killer and suppressor cells as well as their differences from Ly 1+ helper cells.

Animals↗