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Biomedical subjects

H D Engers

Publications and source records attributed to H D Engers.

At least 37 records · Page 2Linked to original sources
PubMed1984

Functional activity in vivo of effector T cell populations. II. Anti-tumor activity exhibited by syngeneic anti-MoMULV-specific cytolytic T cell clones.

The functional activity in vivo of murine tumor-specific cytolytic T lymphocyte populations and clones was studied. Tumor cell destruction induced after the i.v. injection of cytolytic effector cells was quantitated by monitoring the elimination of 131IUdR-labeled tumor cells in the peritoneal cavity by using whole-body counting techniques. Mixed leukocyte-tumor cell cultures were established by using spleen cells from C57BL/6 regressor mice that had rejected an intramuscular tumor induced by the injection of MSV-MoMuLV virus. This effector cell population was observed to eliminate syngeneic MoMuLV-induced tumor cells in a dose-dependent manner. Treatment of the effector cell population with monoclonal anti-Lyt-2 antibodies plus complement totally abrogated their ability to induce tumor cell destruction in the peritoneal cavity. MSV-MoMuLV-specific Lyt-2+ cytolytic T cell clones derived by micro-manipulation of T lymphocyte-tumor cell conjugates were also tested for functional activity in vivo. Several clones induced a rapid, specific elimination of 131I-labeled MBL-2 tumor cells from the peritoneal cavity after i.v. injection, whereas others were inactive. Both active and inactive clones were highly cytolytic and secreted MAF/IFN-gamma lymphokines. In contrast to previous results obtained in a tumor allograft model, the MSV-MoMuLV-specific cytolytic T cell clones that were active in vivo did not proliferate in vitro in response to stimulation with irradiated tumor cells plus filler spleen cells in the absence of an added source of interleukin 2.

Animals↗
PubMed1984

Differential effects of two anti-apo-cytochrome c-specific monoclonal antibodies on the function of apo-cytochrome c-specific murine T cell clones.

A murine monoclonal antibody (SJL 2-4) specific for the antigen apo-cytochrome c was shown to inhibit both antigen-induced proliferation and lymphokine secretion by an apo-cytochrome c-specific BALB/c helper T cell clone. The inhibition was specific because additional apo-cytochrome c-specific T cell clones were not inhibited by the same monoclonal antibody. Time course studies of the inhibition indicated that the initial 8 hr of contact between T cell clones and antigen-presenting cells were critical for activation of the T cell clones. Inhibition of T cell functions by antigen-specific antibodies appeared to correlate with the antibody-antigen binding constant because a second monoclonal antibody (Cyt-1-59), with identical specificity but with a lower affinity constant for apo-cytochrome c, had very little inhibitory effect on the proliferation or lymphokine secretion of apo-cytochrome c-specific T cell clones.

Animals↗
PubMed1983

Fine specificity of a BALB/c T cell clone directed against beef apo cytochrome c.

A BALB/c cloned T cell line directed against beef apo cytochrome c was shown to exhibit the Lyt-1+2- cell surface phenotype. The fine specificity of antigen recognition exhibited by the T cell clone was assessed by using a variety of peptide preparations obtained from cytochrome c of different sources. The peptide segment recognized by this T cell clone, in conjunction with I-A region gene products, appeared similar to that bound by a monoclonal antibody specific for beef apo cytochrome c derived from the same strain of mice.

Amino Acid Sequence↗
PubMed1983

Clonal analysis of T cell unresponsiveness to alloantigens induced by neonatal injection of F1 spleen cells into parental mice.

Alloantigen-specific T cell precursors present in spleen cell populations obtained from parental mice that were rendered tolerant by the neonatal injection of F1 spleen cells were quantitated by clonal analysis, i.e., limiting dilution techniques. The results demonstrate that the frequencies for cytolytic as well as TCGF-producing (helper) and MAF-producing T cell precursors were dramatically reduced in tolerant spleen cell populations. The unresponsive state was antigen specific and could not be transferred in vitro in cell mixing experiments. Therefore, clonal deletion (or inactivation) would appear to represent a major mechanism for the observed tolerant state in this model system.

Animals↗
PubMed1983

Prevention of cerebral malaria by adoptive transfer of malaria-specific cultured T cells into mice infected with Plasmodium berghei.

Murine T cell populations specific for Plasmodium berghei parasites were generated in vitro from BALB/c immune lymph node cells. The malaria-specific T lymphocytes were shown: a) to proliferate specifically in vitro in response to stimulation with P. berghei-infected red blood cells; b) to exhibit the Thy-1+, Lyt-1+2- cell surface phenotype; c) to provide specific helper activity for an in vitro anti-hapten (TNP) plaque-forming cell antibody response; and d) to protect P. berghei-infected mice from early mortality due to cerebral malaria.

Animals↗
PubMed1982

Allogeneic tumor rejection induced by the intravenous injection of Lyt-2+ cytolytic T lymphocyte clones.

The in vivo activity of murine Lyt-2+ cytolytic T lymphocyte clones was assessed in a tumor allograft model system. Mice that had been sublethally irradiated 16 h previously were injected intraperitoneally with 131I-IUdR-labeled tumor cells. Simultaneously, various doses of four cytolytic T cell clones were injected intravenously and the mice monitored for tumor cell elimination by whole-body counting tecniques. These four clones had been selected on the basis of their ability to proliferate in response to alloantigens in the absence of added T cell growth factor(s). With two of the four clones tested, rapid elimination of tumor cells within the peritoneal cavity was observed, as early as 48 h after intravenous injection of the cloned T cells.

Animals↗
PubMed1982

Functional activity in vivo of effector T cell populations. I. Antitumor activity exhibited by allogeneic mixed leukocyte culture cells.

The in vivo activity of murine cytolytic T lymphocyte-containing effector cell populations generated in vitro was studied in a tumor allograft model system by monitoring the elimination of 131I-IUdR-labeled tumor cells with whole-body counting techniques. Mice were irradiated sublethally and 16 hr later 131I-labeled tumor cells were injected either subcutaneously or i.p. Simultaneously, graded doses of various effector cell populations were injected i.v. and the mice were counted daily to assess the potential elimination of the radiolabeled tumor cells. Thus, allogeneic 2 degrees mixed leukocyte culture cells were observed to eliminate allogeneic but not syngeneic tumor cells in a dose-dependent manner, with as few as 0.2 x 10(6) effector cells causing significant destruction of 2 x 10(6) allogeneic tumor cells. The protective effect of the mixed leukocyte culture cells was considerably reduced when Lyt-2+-bearing lymphocytes were eliminated by treatment with monoclonal antibody plus complement. In additional experiments, Lyt-2+ lymphocytes positively selected by enrichment on antibody-coated petri dishes gave efficient protection, in the absence of Lyt-2- cells. Surprisingly, when several different cloned, specific, long-term allogeneic cytolytic T cells lines were injected either i.p. of i.v., tumor cell destruction was observed only after i.p. injection.

Animals↗
PubMed1981

Characterization of an immunosuppressive parvovirus related to the minute virus of mice.

We have characterized an immunosuppressive parvovirus related to the minute virus of mice (MVM). The parvovirus, MVM(i), grew efficiently on the murine lymphoma cell line EL-4 and not on the A-9 strain of L-cells which is a host for the prototype MVM. MVM(i) was immunosuppressive for allogeneic mixed leukocyte cultures, inhibiting the generation of cytolytic T lymphocytes. MVM had no effect on mixed leukocyte cultures. MVM and MVM(i) particles were similar in buoyant density, sedimentation rate, appearance in the electron microscope, and polypeptide composition. We present restriction enzyme maps of the DNAs of MVM and MVM(i) which show that they are closely related. Out of 109 restriction endonuclease cleavage sites (representing together about 10% of the nucleotide sequence), 86 sites were shared by MVM and MVM(i), whereas 22 sites were absent from one of the two viruses. MVM(i) DNA had an apparent deletion of about 60 nucleotides relative to MVM, located near the 5' terminus of viral DNA.

Animals↗
PubMed1981

Clonal analysis of the BALB/c T cell proliferative response to apo beef cytochrome c.

Murine T cell clones that proliferated specifically in response to the protein antigen apo cytochrome c were derived and maintained in continuous culture. Two distinct clonotypes were observed with respect to the proliferative responses observed when a variety of peptides prepared from several species of cytochrome c were tested. These 2 clonotypes appeared to recognize 2 different regions in the cytochrome c molecule. Only 1 of the 2 clonotypes tested demonstrated helper cell activity for antibody formation in vitro.

Animals↗
PubMed1981

Recognition of protozoan parasites by murine T lymphocytes. II. Role of the H-2 gene complex in interactions between antigen-presenting macrophages and Leishmania-immune T lymphocytes.

The proliferative response of nylon wool purified, primed lymph node cells to L. tropica parasites in vitro was found to be restored by the addition of either syngeneic or allogeneic adherent spleen cells as a putative source of macrophages. These results suggested a lack of H-2 restriction in Leishmania-specific T cell responses. However, when T cell blasts generated in vitro in response to the parasite were separated on Percoll density gradients and subsequently maintained for 4 days in the presence of TCGF, their response to L. tropica was found to be strictly dependent on the presence of syngeneic spleen cells. Further studies using congenic recombinant mice demonstrated that proliferation of a parasite-specific blasts required the presence of spleen cells compatible with the responding cells in the I-A region of the MHC. This requirement for I-A compatible adherent cells in the spleen cell populations was further confirmed by a lack of proliferative responses in the presence of spleen cells treated with monoclonal anti-la antibodies and complement. Leishmania-immune F1 blasts responding to the parasite in the context of either parental la-bearing accessory cell could be obtained by positive selection from a F1 hybrid responding cell population. Using flow microfluorometry, the T cell phenotype of the L. tropica-specific blasts was determined to be Thy-1+, lyt-1+, and Lyt-2-.

Animals↗
PubMed1981

Inhibition of T cell-mediated functions by MVM(i), a parvovirus closely related to minute virus of mice.

A purified preparation of MVM(i), a murine parvovirus closely related to minute virus of mice (MVM), was found to inhibit various functions mediated by murine T cells in vitro. Addition of MVM(i) virus to secondary allogeneic mixed leukocyte cultures resulted in the inhibition of both lymphocyte proliferation (3H-thymidine incorporation) and the generation of cytolytic T lymphocyte activity but not interferon production. MVM(i) virus also inhibited the growth and cytolytic activity of several cloned, long-term Lyt-2+ cytolytic T cell lines. Furthermore, the antigen-induced proliferative responses of parasite- (Leishmania) specific Lyt-1+ T cells in vitro was abrogated by the addition of MVM(i) virus to the culture. Finally, the suppression of an in vitro antibody response to SRBC by MVM(i) virus was the result of the inhibition of T helper cells required for the B cell response. These suppressive effects were specific for MVM(i); parallel studies in which the prototype MVM parvovirus was used showed no significant inhibition in the various systems tested.

Animals↗
PubMed1980

Interferon production by human and murine lymphocytes in response to alloantigens.

The production of interferon (IF) by human and mouse lymphocytes sensitized to alloantigens in mixed lymphocyte cultures (MLC) was analyzed. During primary MLC, IF appeared in the culture fluid on day 2 and was maximal on day 5. Based on several biologic criteria, the IF produced is of the "immune" type. When lymphocytes sensitized to alloantigens were reestimulated in vitro, IF was produced within a few hours of culture. In all stimulated cultures, cell proliferation was observed in spite of the high concentrations of IF. The IF-producing cells in human MLC were identified as T lymphocytes lacking the receptor for the Fc fragment of IgG molecules (Fc gamma R(-)). Human MLC supernatants containing immune type IF mediate the enhancement of natural killer (NK) cell activity and protect NK target cells from lysis.

Animals↗
PubMed1980

Characterization of cloned murine cytolytic T cell lines.

Murine cytolytic T lymphocytes can be kept in continuous culture apparently indefinitely by repeated passage in a concanavalin A-induced growth promoting medium. Some of these long-term cell lines maintain their cytolytic activity. Starting from three such populations, several cloned cytolytic T cell lines were derived and subsequently subcloned one or more times. Considerable variation in the levels of cytolytic activity was observed between different subclones; some initially active subclones lost activity with prolonged culture. In addition, one of the clones appeared to progressively lose the relative specificity demonstrated during the earlier passages of the parent cell line.

Animals↗
PubMed1979

An estimate of the minimal frequency of cytolytic T lymphocyte effector cells generated in allogeneic reactions.

A 'micro' modification of the standard 51Cr release assay was developed. With this assay, significant cytolysis was obtained employing 100--200 51Cr-labeled target cells and fewer than 100 lymphocytes obtained from mixed leukocyte cultures. A minimal estimate as to the actual frequency of effector cells was determined for both primary (1 cell in 30) and secondary (1 cells in 8) cytolytic T lymphocyte populations.

Animals↗