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Biomedical subjects

F H Bach

Publications and source records attributed to F H Bach.

At least 325 records · Page 18Linked to original sources
PubMed1983

The cellular mechanism of maintenance of neonatally induced tolerance to H-2 class I antigens.

We used limiting dilution analysis protocols to investigate the mechanism by which in vitro cytotoxic T lymphocyte (CTL) hyporeactivity is maintained in adult mice that had been neonatally tolerized to major histocompatibility complex-encoded antigens. Class I molecules, presented on donor cells having an H-2 K or D region haplotype difference from recipients, readily induce tolerogen-specific CTL hyporeactivity. All attempts to identify any in vitro effects of active suppressive cells operative in the maintenance of this hyporeactivity have been unsuccessful. We conclude that this cytotoxic deficiency is the consequence of in vivo mediated clonal inactivation of the precursors of tolerogen-specific CTL. A presentation and evaluation of the assumptions inherent in this conclusion are made. In contrast to class I molecules, class II molecules, presented on donor cells having an H-2 I region haplotype difference from recipients, are unable to induce tolerogen-specific CTL hyporeactivity, even when injected neonatally at high doses. This inability of class II molecules to induce CTL tolerance parallels the considerable difficulty of inducing helper T lymphocyte tolerance to class II molecules.

Aging↗
PubMed1983

Response against single minor histocompatibility antigens. I. Functional and immunogenetic analysis of cloned cytolytic T cells.

A clonal approach was used to investigate the cellular basis of a T cell response to single minor histocompatibility antigens (miHA). This analysis was performed by functional and immunogenetic characterization of a large number of clones derived from short-term mixed leukocyte culture (MLC) populations generated against the miHA, H-1.3. Forty-nine clones isolated from such MLC were specifically cytolytic for H-1.3-bearing, H-2Db-compatible target cells. Thirty-seven of the 49 cytolytic clones were driven to proliferate when stimulated by spleen cells bearing the H-1.3 alloantigen in the absence of added T cell-derived growth factor(s) (GF). The remaining 12 clones proliferated only when GF was added. A strong positive correlation was observed between antigen-induced proliferation and the production of interleukin 2 (IL 2) activity. A similar correlation was observed when comparing the ability of both antigen and concanavalin A to induce IL 2 activity from the clones. These data suggest that i) antigen-driven or helper T cell-independent cytolytic T cells (HITc) are frequent components of an MLC response to a single miHA, and ii) the ability of HITc to undergo antigen-driven proliferation is related to their ability to produce antigen-induced GF.

Animals↗
PubMed1983

Dissociation in expression of MB1/MT1 and DR1 alloantigens in mutants of a lymphoblastoid cell line.

Cytotoxicity tests with alloantisera were used to study the expression of HLA-D region antigens in HLA-DR-null mutants of a human lymphoblastoid cell line. The initial cell line contained just one copy of the MHC as a haplotype that included DR1 and MB1/MT1. Gamma ray mutagenesis of the single haplotype cells followed by selection with complement and an anti-DR monoclonal antibody were then used to isolate DR-null mutants. Two categories of mutants were identified with a panel of alloantisera. Expressions of DR1 and MB1/MT1 were simultaneously lost in four mutants. Nine mutants still expressed MB1/MT1 but had lost the expression of DR1. The dissociated loss of expression of MB1/MT1 and DR1 antigens is evidence for separate genetic control of these alloantigens. The methods used exemplify a versatile approach for conveniently inducing separations of closely linked loci of the MHC.

Cell Line↗
PubMed1983

Phorbol ester mediates reversible reduction of cloned T lymphocyte cytolysis.

Prolonged contact with nanomole to micromole concentrations of the tumor promoter phorbol myristate acetate causes a significant reduction in the lytic activity of cloned cytolytic T cells. Diminished lysis is apparent even in the presence of agglutinating lectins. PMA does not exert this effect by minimizing clone viability. In fact, these concentrations of PMA cause significant potentiation of antigen-driven proliferation for many of these same clones. The PMA-mediated loss of cytolysis is reversible. Although contact with antigen does not induce or enhance reexpression of cytolysis, PMA-treated cytolytic T cell clones display normal cytolytic activity after contact with lymphokines.

Animals↗
PubMed1983

HLA antigens in renal cell carcinoma.

HLA antigen type was studied in 35 renal cell carcinoma patients who had bilateral disease, an early age of onset (less than age 45), or a family history of kidney cancer. Increased frequencies of the single-locus antigens HLA-DR8 (relative risk, 3.3) and HLA-Bw44 (relative risk, 2.1) and a deficit of HLA-DR1 (relative risk, 0.4) were found. Although based on small numbers, the relative excess was highest among persons phenotypically HLA-Bw44DR8. A higher frequency of the three-locus phenotype HLA-A3B7DR2 was also noted. The unusual HLA patterns were most pronounced among patients of German or Scandinavian origin, population groups reported to have an elevated risk of renal cancer.

Adenocarcinoma↗
PubMed1982

Helper cell-independent cytotoxic clones in man.

We report here a class of helper cell-independent cytotoxic T cell (HITc) clones in man that can proliferate in response to antigenic stimulation as well as mediate cytotoxicity. HITc appear to be rare among clones derived from primary in vitro allosensitized culture, but constitute the majority of clones derived from cells sensitized to autologous Epstein-Barr virus-transformed lymphoblastoid cell lines. The implications of the derivation and function of HITc clones are discussed.

Cell Line↗
PubMed1982

Histocompatibility and isoenzyme differences in commercially supplied "BALB/c" mice.

BALB/c mice obtained commercially were found to differ significantly from the standard phenotype of BALB/c strain mice. Isoenzyme tests and H-2 haplotype analyses indicated that the majority of mice from two of the three sources tested appeared mixed, frequently heterozygous, and did not consistently express either the expected H-2 or glucose phosphate isomerase type.

Animals↗
PubMed1982

Five HLA-D clusters associated with HLA-DR4.

In order to investigate the HLA-D clusters associated with DR4, 54 DR4-positive, Dw4- and Dw10-negative responders, together with selected Dw4- or Dw10-positive responders, were tested with 22 HTCs that define DR4-associated D specificities. The results are consistent with previous data defining four distinct D clusters--Dw4, Dw10, DB3, and DYT--and have identified a new cluster provisionally termed LD40. In addition, the DB3 cluster is complex and appears to give typing response patterns overlapping those of the KT2 cluster originally defined as being associated with DR4 in Japanese populations. Of 116 DR4-positive haplotypes tested, 44% typed as Dw4, 18% were LD40, 16% were Dw10, 9% were DB3, 3% were DYT, and 10% gave no typing response to the HTCs defining any of these clusters. These studies are informative not only in defining the DR4-associated D clusters and in supporting the concept that D and DR cannot be considered identical but also in emphasizing the complexity of the D region.

Asian↗
PubMed1982

Cloned cellular reagents to define antigens encoded between HLA-DR and glyoxylase.

Primed lymphocyte typing reagents have been used to define antigens encoded by genes of a locus (loci) mapping between HLA-DR and glyoxalase I. This locus, which we shall refer to as the third locus of the HLA-D region, has been variously referred to as D beta, PL beta, PL3, and SB. Generating discriminatory primed lymphocyte typing reagents which can be used to define these antigens, however, has been extremely difficult. Donors of responding and stimulating cells for the priming combinations have usually been matched not only for the DR, D, and MB/MT antigens but also for the HLA-A, -B, and -C antigens. Even under these very restricted conditions, not all bulk primed lymphocyte typing reagents that are generated are discriminatory enough to be useful for antigen definition. We have derived "clones" from bulk priming combinations in which stimulator and responder differed for known antigens of this third locus. Even though the bulk reagents that were prepared did not provide discriminatory results, approximately 7-12% of the clones derived from the bulk priming combination proved to be highly discriminatory. We have been able to obtain these results with regard to all three antigens of the third locus so far evaluated. The very ease of screening clones and deriving discriminatory reagents, as compared with screening responder-stimulator combinations, allows the ready derivation of cellular reagents that define the antigens of this third locus.

Antibody Formation↗
PubMed1982

Genetic heterogeneity of diabetes and HLA.

Histocompatibility (HLA) antigens and genotypes B, D and DR were studied in large sample of Caucasian insulin dependent diabetic (IDD) probands. The associations between IDD and B8, B15, Dw3, Dw4, and DR3, and DR4 were measured by relative risks (RR) and delta values. Both the homozygotes (B8/8: RR 10, B 15/15: RR 7, DR3/3: RR32, DR4/4: RR34) and the heterozygotes (B8/15: RR 11, DR3/4: RR22) for the high-risk antigens showed highly significant elevation of the relative risks, yet there were no statistically significant differences between the homo- and the heterozygotes. The delta measurements supported the RR results. RR and delta were found significantly decreased for B7, Dw2, and DR2. There were no relationships observed between age at diagnosis or family history and HLA. Although we were unable to demonstrate a statistically significant difference between the RR for the high-risk antigens heterozygote vs. the high-risk antigen homozygotes, our study like many others shows that the RR is higher for the heterozygotes. Thus our data are compatible with genetic heterogeneity of IDD.

Adolescent↗
PubMed1982

HLA and susceptibility to type I diabetes. Hypothesis.

Positive associations between the antigens D(R)3 and D(R)4 and negative associations of D(R)2 have been reported with insulin dependent or type I diabetes mellitus. It has been suggested that susceptibility factor(s) associated with the D(R)3 and D(R)4 haplotypes and a resistance factor associated with the D(R)2 haplotype may be involved in the pathogenesis of the disease. We propose a hypothesis herein which attempts to unify these findings based on our present understanding suggesting (a) the existence of multiple antigenic determinants associated with any one D(R) haplotype and (b) the sharing of "single" D region encoded determinants between what we now refer to as different D(R) haplotypes. The hypothesis, in its simplest form, focuses on a single D region determinant which can be found associated at different frequencies with the various D haplotypes as potentially explaining the findings.

Diabetes Mellitus↗
PubMed1982

Analysis of cloned T cell function. I. Dissection of cloned T cell proliferative responses using cyclosporin A.

CsA interferes in a specific manner with the expansion of T cell clones in that it inhibits the antigen-driven component of the proliferative responses made by cloned helper T cells, cloned conventional cytolytic T cells, and cloned helper-independent cytolytic T cells. Cloned helper T cells and helper-independent cytolytic T cells, which share the ability to proliferate when cultured with specific alloantigen, fail to proliferate when cultured with specific alloantigen, fail to proliferate in response to this stimulus in the presence of CsA (10 to 100 ng/ml). In contrast, the proliferation observed when these cells are cultured with exogenous growth factors (but not alloantigen) is little influenced by as much as 1000 ng/ml CsA. When cloned helper T cells or helper-independent cytotoxic T cells are cultured with alloantigen plus exogenous growth factor, additive or synergistic proliferation occurs. However, CsA (10 to 1000 ng/ml) blocks only the component of proliferation induced by alloantigen, and leaves the lymphokine-driven component intact. CsA has similar effects on the proliferation of cloned conventional cytolytic T cells. Thus, CsA separates cloned T cell proliferation into two components: one driven by contact with alloantigens, the other driven by contact with mitogenic lymphokines.

Animals↗
PubMed1982

Successful transplantation of a human leukemia cell line into nude mice: conditions optimizing graft acceptance.

Conditions were determined for successful subcutaneous tumor development of MOLT-4 human T-cell leukemia cells in BALB/c nude (nu/nu) female mice. MOLT-4 cells injected alone at one site resulted in tumors in none of 21 mice, whereas MOLT-4 cells injected with X-irradiated human fibrosarcoma cells (HT-1080) at another site resulted in tumors in 5 of 21 mice. When X-irradiated three times with 200 rad over a 3-week period and then inoculated with MOLT-4 cells and X-irradiated HT-1080 cells, 19 of 25 mice developed tumors, which indicated that a combination of X-irradiation of the recipients and inoculation of an admixture of the leukemia cells with X-irradiated fibrosarcoma cells markedly increases tumor incidence. The cells growing in the tumors had the characteristics of MOLT-4, as assessed by marker studies and histology.

Animals↗