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M C Simmler

Publications and source records attributed to M C Simmler.

34 records · Page 2Linked to original sources

Minor histocompatibility antigens are developmentally regulated on murine embryonal carcinoma cells and their early differentiated derivatives.

Differences in the expression of minor histocompatibility (Hm) alloantigens on two mouse embryonal carcinoma (EC) cell lines and the PYS-2 and T.D.M.-1 differentiated derivatives have been demonstrated by their ability to elicit a cytolytic T lymphocyte response. Experiments involving the use of various responder-target strain combinations and recombinant inbred mice strains have shown that: (1) there are major differences in Hm expression on EC cells compared with differentiated derivatives whose Hm expression appears more like that of adult splenocytes; (2) although both EC cell lines show reduced Hm immunogenicity compared with adult splenocytes, major differences in the expression and possible presentation of Hm between the F9 and PCC3 EC cell lines can be detected by in vivo priming and by in vitro cold competition target experiments. These observations are discussed in relation to the differences in allograft rejection patterns observed with PCC3 and F9 and to possible differences in developmental staging of these cell lines.

Animals↗

Genetics of teratocarcinoma transplantation. III. Genetic control of resistance to F9 tumor formation in allogeneic hosts.

Major F9 allograft resistance of strains C57Bl/6J, CBA/J, C3H/He and AKR/J has been shown to be controlled by a small number of recessive genes. These loci are not linked to H-2. Recombinational analysis suggests that the loci responsible for resistance in these strains are at least partially non-overlapping. These results obtained with the blocked F9 embryonal carcinoma cell line are discussed in relation to those reported for embryonal carcinoma strain PCC3/A/l and OTT6050 embryoid bodies, where recessive resistance is H-2 linked.

Animals↗

The significance of natural killer activity in the resistance of allogeneic hosts to the embryonal carcinoma cell line F9.

A number of mouse strains of known F9 resistance phenotype have been tested for their in vitro natural killer activity against both F9 and YAC target cells. The pattern of in vitro natural killer activity observed does not correlate with the pattern of in vivo F9 resistance. The relative efficiencies of in vitro lysis of the F9 and YAC targets by endogenous natural killer effectors from the 129/Sv, SJL/J, C57Bl/6J, and BALB/cJ strains do, however, parallel each other, even though overall levels of F9 target lysis are very low. Since cold competition experiments indicate that the embryonal carcinoma cell lines tested, F9, PCC4/Aza, and PCC3/A/1, can compete efficiently with YAC as target, this low lysis of embryonal carcinoma cells may be due to an intrinsic lysis resistance. The finding that the parietal endoderm cell line PYS-2 and the trophoectodermal cell line TDM1 also compete with YAC targets in cold competition experiments is discussed in relation to previous reports suggesting that such differentiated derivatives lack natural killer target structures.

Animals↗

Accessory cells in the in vitro generation of type C virus-specific T killer lymphocytes. II. Demonstration of a T helper cell in the spleen of in vivo primed mice.

The existence of a helper T cell cooperating with cytolytic T lymphocytes (CTL) in cell-mediated anti-tumor responses specific for the virus-induced FMR antigens can be demonstrated by using unprimed thymocytes as CTL precursors and in vivo primed irradiated spleen cells as helper. The helper T cells express Thy-1.2 and Lyt-1.2 antigens at their surface, but not Lyt-2.2. The helper function required the presence of macrophages to be detected, is antigen specific, and appears unusually radiosensitive compared with previously described helper T cell function.

Animals↗

Comparison of the restoration effect of Pseudomonas aeruginosa, BCG and poly I: poly C on cancer patients non responsive to recall antigen delayed hypersensitivity.

A preparation of 10 serotypes of Pseudomonas aeruginosa has restored skin delayed hypersensitivity reactions to recall antigens in about fifty per cent of cancer patients not previously immunodepressed by radiotherapy or chemotherapy, but anergic. This proportion is similar to that obtained by given modalities of administration of BCG, C. parvum or levamisole, while other modalities of application of BCG or administration of poly I: poly C do not induce such an immuno-restoration in a significant number of patients.

BCG Vaccine↗

Modulation by alpha-2 macroglobulin of human lymphocyte proliferation in response to mitogens and antigen.

The effect was studied of purified alpha-2 macroglobulin (a potent and polyvalent protease inhibitor) on normal human lymphocytes stimulated by phytohaemagglutinin, pokeweed mitogen, or by purified protein derivative as an antigen. At physiological concentration alpha 2 M has been found to inhibit mitogenic as well as antigenic stimulation. However at lower dilutions alpha 2 M acts in synergy either with the mitogen or with the antigen. At these dilutions thymidine incorporation is enhanced. alpha 2 M has no toxic or mitogenic effect on normal human lymphocytes. These data might indicate that two proteases may play a role in the proliferation of normal human lymphocytes.

Antigens↗

Cell-mediated immune responsiveness of patients with acute lymphocytic leukemia in remission.

Children with acute lymphocytic leukemia (ALL) in remission and undergoing either chemotherapy or immunotherapy were tested for general cell-mediated immunocompetence and cell-mediated reactivity to tumor-associated antigens (TAA) using the following parameters: skin tests with recall antigens and extracts of lymphoblastoid cell lines; primary sensitization to dinitrofluorobenzene and picryl chloride; in vitro tranformation by mitogens and PPD; and lymphocyte-mediated cytotoxicity against a lymphoblastoid cell line and a panel of cryopreserved leukemic blasts. Reactivity in all assays of children on continuous chemotherapy was significantly depressed compared to similar patients later in the study. Patients on intermittent chemotherapy demonstrated much less immunodepression. The groups tested early during immunotherapy with BCG and allogeneic leukemic blasts were hyper-responsive (compared to published data) to primary sensitization with picryl chloride. Skin test reactivity to recall antigens and to tumor-derived lymphoblastoid cell lines was suppressed (as analyzed serial comparison) in this hyperimmunized group, possibly due to antigenic competition, and reactivity in all other assays was normal. The patients tested after 2-8 years of immunotherapy showed significantly higher positive skin-test responses to extracts of tumor-derived lymphoblastoid cell lines as compared to the other groups. The results of this multiphasic screen support the known effects of chemotherapy on immunocompetence. Moreover, they document the prompt return of immunocompetence with intermittent chemotherapy and during immuno-therapy. These results do not, however, indicate a striking augmentation of the immune response during immunotherapy as measured by these parameters.

Antigens, Bacterial↗

Pseudoautosomal DNA sequences in the pairing region of the human sex chromosomes.

A DNA probe from a human Y chromosome-derived cosmid detects a single-copy genomic DNA fragment which can appear in different allelic forms shared by both sex chromosomes. Variants at this DNA locus show an autosomal pattern of inheritance, undergo recombination with sexual phenotype and can therefore be described as 'pseudoautosomal'. Another probe from the same cosmid detects a sequence repeated 15-20 times per haploid genome. These repeats also appear pseudoautosomal and map exclusively to the short-arm terminal region of each sex chromosome.

Chromosome Mapping↗

A gradient of sex linkage in the pseudoautosomal region of the human sex chromosomes.

Three independent pseudoautosomal loci are linked to sex determination at frequencies which define a gradient of linkage. The segregation patterns of these loci indicate that X/Y recombination results from a single obligatory meiotic crossing-over in the pseudoautosomal region. Recombination in male germ cells in the terminal regions of the short arms of the X and Y chromosomes in 10-fold greater than between the same regions of the X chromosomes in female germ cells.

Animals↗

Monitoring of nonspecific cell-mediated immunity in cancer patients. I. Frequent dissociation between the responses of skin tests to recall antigens and in vitro lymphocyte transformation.

No correlation was found between in vivo delayed hypersensitivity responses in cancer patients and in vitro lymphocyte transformation by mitogens or antigens, even when the same antigen [purified protein derivative of tuberculin (PPD)] was used for both the in vivo and in vitro testing. However, there was a good correlation between the in vitro lymphocyte transformation tests with PPD and with the mitogens phytohemagglutinin and pokeweed mitogen.

Adolescent↗