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F H Bach

Publications and source records attributed to F H Bach.

At least 415 records · Page 23Linked to original sources

Genetic basis of memory in cell-mediated immune response.

The present experiments were undertaken to delineate the role of LD and SD antigens in terms of memory in cell-mediated immune response (CML). Using recombinants that differ for either the H-2K or H-2D determinants (SD-different) and other recombinants differing for the central region of H-2 (LD-different), we have investigated this question. The results indicate that priming to SD determinants leads to a more rapid and higher response when cells are restimulated in vitro with either the same SD antigen alone or the same SD plus an LD antigen and tested on target cells that possess either the SD antigen alone or both the LD and SD antigen. Antigens in the central regions of H-2, which includes LD, serve as the stimulus both for the helper T cells and for the cytotoxic T lymphocytes. Priming with a high dose of LD antigens leads to memory in the cytotoxic T lymphocyte recognizing the cytotoxic target antigens coded by the central region of H-2. Nevertheless, memory could not be detected when priming was done under the same conditions as for SD antigens. Moreover, a primed helper T-cell response does not facilitate the development of increased CML on restimulation in vitro with the LD antigen used for priming and a new SD antigen. Thus, it seems that memory in CML is in the cytotoxic T lymphocyte and not in the proliferating helper cells.

Animals↗

Primed LD typing: reagent preparation and definition of the HLA-D-region antigens.

Primed LD typing cells were prepared against single HLA haplotypes within families and used to type a random panel of 48 individuals. PLT cells could be grouped on the basis of highly correlated responses with the panel test cells; the 21 different PLT cells could be used to define 6 different PL antigens. One of these, PL 3, was split by the responses of two of the 21 PLT cells which measured an antigen called PL 3.1.

Epitopes↗

Response of primed LD typing cells to homozygous typing cells.

At least two different methods using cellular responses have been described for defining the determinants of the HLA-D region: typing with HLA-D homozygous cells and primed LD typing. Primed LD typing cells were generated in one-haplotype-different combinations and grouped on the basis of two or more cells appearing to define the same HLA-D-region-determined PL antigen. Such cells were restimulated with homozygous typing cells for several of the presently known HLA DW clusters. A very strong correlation was noted: PLT cells defining the antigen PL1 were restimulated with homozygous typing cells for DW3, those PLT cells defining the antigen PL2 were restimulated by homozygous typing cells for DW2, and those defining PL5 were restimulated by homozygous typing cells for DW1.

Epitopes↗

Typing an unrelated panel with PLT cells: association with DW clusters.

Primed LD typing (PLT) cells prepared in one Laboratory (Madison) were shipped in the frozen state and tested in Tübingen on a separate panel that had been typed with homozygous typing cells. Those PLT cells that had been grouped, on the basis of their reaction with test cells of the Madison panel, as defining an HLA PL antigen showed identical or nearly identical patterns of reactivity with the Tübingen panel. Clear association between certain PL antigens and DW clusters as defined with homozygous typing cells could be demonstrated. Of particular interest may be combinations of certain PLT reactions with D-locus-typed cells, where the primed cells do not react as expected from the target's HLA-D type.

Epitopes↗

Lack of restimulation by non-HLA antigens in primed lymphocyte typing.

We have studied the role of non-HLA antigens in restimulation of PLT cells by the following protocols. Responder cells were sensitized to cells from family members differing by one HLA haplotype. The PLT cells were restimulated by family members HLA- or HLA-D-identical to the responder. In none of these cases did we find significant restimulation, indicating that it is unlikely that there is a restimulatory non-HLA locus with even two alleles (p less than 0.05) of equal frequency. Other protocols we have used are consistent with this interpretation. This indicates that antigens determined by genes segregating independently of HLA do not play a major role in the PLT restimulation.

Antigens↗

Tolerance induction to H-2 central region target antigens: in vivo/in vitro correlations.

Tolerance was induced against cytotoxic target determinants coded for by genes of the I region. Neonatal recipients were immunized with high doses of cells from an I region incompatible donor. Nonreactivity in adult life did not reflect extensive donor cell chimerism, since the great majority of cells in spleens of animals rendered tolerant were of host phenotype. Although specific nonresponsiveness in CML could be induced by these protocols, the MLC proliferative response was in most cases still present alghough very much decreased. In only a very occasional animal was complete nonreactivity in MLC seen. The nonresponse in CML was paralleled by acceptance of thyroid allografts as measured by radioactive iodine incorporation and morphological studies.

Animals↗

Lymphoblastoid cell lines of homozygous typing cells used for sensitization in PLT.

Lymphoblastoid cell lines of homozygous typing cells were used as the sensitizing cells in MLC to prepare PLT cells. Results obtained using such cells against a panel of restimulating cells were compared to those obtained using regular PLT cells in which priming had been accomplished with normal peripheral blood lymphocytes. It appears that lymphoblastoid cell lines can be used for this purpose; the advantages of such an approach are given.

Cell Line↗

Antigenic requirements for the generation of secondary cytotoxicity.

The in vitro role of products of the H-2 complex in restimulation of secondary proliferative and cytotoxic responses has been studied. In this paper we have studied in particular the role of CD antigens, the target antigens for cytotoxic T lymphocytes. We have used UV-treated cells that express their CD antigens but no LD. Like others, we demonstrate that CD antigens alone are able to generate a secondary cytotoxic response and furthermore that these CD antigens must be the same as those used for primary sensitization. However, in contrast to the results of others, in some cases UV-treated cells were unable to restimulate such a response even when appropriate controls showed that the CD antigens on UV-treated cells were functional. Furthermore, in these cases the addition of an LD stimulus in the presence of UV-treated cells results in a secondary cytotoxic response that is significantly greater than that elicited by LD restimulation alone. Such potentiation is not observed if the CD antigens used for restimulation are different from those used for the primary sensitization. In addition, a non-H 2 differences(s), presumably the M1s locus, appears to be able to generate a secondary response. The implication of these results are discussed in terms of "memory" T lymphocytes in cell-mediated immunity.

Animals↗

Prolonged survival of xenografts after organ culture.

Recent reports demonstrate that culture of thyroid allografts before transplantation results in prolonged and sometimes indefinite survival. The loss of passenger leukocytes during organ culture was discussed as a possible reason for these findings. Recent data from a genetically defined system in the mouse demonstrated that passenger leukocytes play an important role in providing a helper stimulus which potentiates the generation of cytotoxic T cells to serologically defined determinants. To ascertain whether this mechanism also is involved in a xenogeneic system, cultured Wistar thyroids were transplanted to DBA/2 mice. The experimental system used was described first by Lafferty and co-workers. Thyroid function was determined by 125-iodine uptake of the graft and by histology. Fresh Wistar thyroids were rejected after a short period of good function on the sixth day after transplantation. Culturing for 10 days resulted in a prolonged graft function up to the fifteenth day. However, if the thyroids were kept in culture for 27 days, no functional signs of rejection could be detected on the twenty-fifth day after transplantation by iodine uptake. The iodine uptake ratio was 47.1 (control group on day 6 was 2.4). Injection of 10(5) fresh donor cells at the time of transplantation reversed the effect of long-term organ culture.

Animals↗

Specificity and structural analysis of a guinea pig transfer factor-like activity.

A transfer factor-like activity was prepared by Sephadex G-25 chromatography of immune guinea pig leukocyte lysates. This isolated material leads to antigen-dependent migration inhibition and thymidine uptake by nonimmune lymphoid cells. Tests of the "transfer factor" from guinea pigs immunized to either ovalbumin or bovine gamma-globulin demonstrated the donor specificity of the in vitro activity. The activity is susceptible to heat (56 degrees C), alkali (0.5 M sodium hydroxide), pronase, and phosphodiesterase. The pronase susceptibility is blocked by traysylol, a protease inhibitor; the phosphodiesterase susceptibility is not bocked by traysylol. The guinea pig factor was purified further by alkaline phosphatase treatment. Sephadex G-25 chromatography, and DEAE-cellulose chromatography. The final product, active in vitro, represents about 0.03% of the cellular material absorbing 260 nm light, and contains polymerized amines and phosphate. Gel electrophoresis of the fluram-reactive components suggests a limited heterogeneity of the DEAE-cellulose-purified material. These data are consistent with the active "transfer factor" molecule including both peptide and phosphate-containing components.

Alkalies↗