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Title: Lysis of typhus-group rickettsia-infected targets by lymphokine activated killers

Abstract

The authors recently described a subset of OKT8, OKT3-positive lymphocytes from typhus-group rickettsia immune individuals which were capable of lysing autologous PHA-blasts or Epstein-Barr virus transformed B cells (LCL) infected with typhus-group rickettsiae. In order to determine if killing by these effectors was HLA-restricted, they stimulated peripheral blood mononuclear cells (PBMC) from typhus-group rickettsia immune individuals in vitro with typhus-group rickettsia-derived antigen for one week and then measured lysis of autologous LCL or HLA-mismatched LCL in a 4-6 hour Cr/sup 51/-release assay. There was significant lysis of both the autologous and the HLA-mismatched infected targets as compared to the corresponding uninfected targets. Since this suggested that the effectors were lymphokine activated killers (LAK) rather than cytotoxic T lymphocytes, they then tested this hypothesis by stimulating PBMC from both immune and non-immune individuals in vitro for one week with purified interleukin 2 and measuring lysis of infected, autologous LCL. PBMC thus treated, from both immune and non-immune individuals, were capable of significantly lysing autologous, infected LCL as compared to the non-infected control. They therefore conclude that targets infected with typhus-group rickettsiae are susceptible to lysis to LAK.

Authors:
;
Publication Date:
Research Org.:
Naval Medical Research Institute, Bethesda, MD
OSTI Identifier:
5506465
Report Number(s):
CONF-8604222-
Journal ID: CODEN: FEPRA; TRN: 86-026730
Resource Type:
Conference
Resource Relation:
Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States); Journal Volume: 45:3; Conference: 70. annual meeting of the Federation of American Society for Experimental Biology, St. Louis, MO, USA, 13 Apr 1986
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; BLOOD CELLS; LYSIS; LYMPHOCYTES; CELL KILLING; RICKETTSIAE; INFECTIVITY; ANTIGENS; BIOLOGICAL FUNCTIONS; CHROMIUM 51; IMMUNE REACTIONS; LYMPHOKINES; TRACER TECHNIQUES; TYPHUS; ANIMAL CELLS; BETA DECAY RADIOISOTOPES; BIOLOGICAL MATERIALS; BLOOD; BODY FLUIDS; CHROMIUM ISOTOPES; CONNECTIVE TISSUE CELLS; DISEASES; ELECTRON CAPTURE RADIOISOTOPES; EVEN-ODD NUCLEI; FUNCTIONS; GROWTH FACTORS; INFECTIOUS DISEASES; INTERMEDIATE MASS NUCLEI; ISOTOPE APPLICATIONS; ISOTOPES; LEUKOCYTES; MATERIALS; MICROORGANISMS; MITOGENS; NUCLEI; ORGANIC COMPOUNDS; PROTEINS; RADIOISOTOPES; RICKETTSIAL DISEASES; SOMATIC CELLS; 550901* - Pathology- Tracer Techniques

Citation Formats

Carl, M., and Dasch, G.A.. Lysis of typhus-group rickettsia-infected targets by lymphokine activated killers. United States: N. p., 1986. Web.
Carl, M., & Dasch, G.A.. Lysis of typhus-group rickettsia-infected targets by lymphokine activated killers. United States.
Carl, M., and Dasch, G.A.. Sat . "Lysis of typhus-group rickettsia-infected targets by lymphokine activated killers". United States. doi:.
@article{osti_5506465,
title = {Lysis of typhus-group rickettsia-infected targets by lymphokine activated killers},
author = {Carl, M. and Dasch, G.A.},
abstractNote = {The authors recently described a subset of OKT8, OKT3-positive lymphocytes from typhus-group rickettsia immune individuals which were capable of lysing autologous PHA-blasts or Epstein-Barr virus transformed B cells (LCL) infected with typhus-group rickettsiae. In order to determine if killing by these effectors was HLA-restricted, they stimulated peripheral blood mononuclear cells (PBMC) from typhus-group rickettsia immune individuals in vitro with typhus-group rickettsia-derived antigen for one week and then measured lysis of autologous LCL or HLA-mismatched LCL in a 4-6 hour Cr/sup 51/-release assay. There was significant lysis of both the autologous and the HLA-mismatched infected targets as compared to the corresponding uninfected targets. Since this suggested that the effectors were lymphokine activated killers (LAK) rather than cytotoxic T lymphocytes, they then tested this hypothesis by stimulating PBMC from both immune and non-immune individuals in vitro for one week with purified interleukin 2 and measuring lysis of infected, autologous LCL. PBMC thus treated, from both immune and non-immune individuals, were capable of significantly lysing autologous, infected LCL as compared to the non-infected control. They therefore conclude that targets infected with typhus-group rickettsiae are susceptible to lysis to LAK.},
doi = {},
journal = {Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)},
number = ,
volume = 45:3,
place = {United States},
year = {Sat Mar 01 00:00:00 EST 1986},
month = {Sat Mar 01 00:00:00 EST 1986}
}

Conference:
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  • Cytolytic human T cells clones generated in response to the intracellular bacterium Rickettsia typhi were characterized. Growing clones were tested for their ability to proliferate specifically in response to antigens derived from typhus group rickettsiae or to lyse targets infected with R. typhi or Rickettsia prowazekii, as measured by /sup 51/Cr-release from target cells. Two clones were able to lyse targets infected with typhus group rickettsiae. One of these clones was more fully characterized because of its rapid growth characteristics. This cytolytic clone was capable of lysing an autologous infected target as well as a target matched for class Imore » and II histocompatibility leukocyte antigens (HLA). It was not capable, however, of lysing either a target mismatched for both class I and II HLA or a target partially matched for class I HLA. In addition, the clone exhibited specificity in that it was able to lyse an autologous target infected with typhus group rickettsiae, but did not lyse an autologous target infected with an antigenically distinct rickettsial species, Rickettsia tsutsugamushi. These results demonstrate, for the first time, that cells infected with intracellular bacteria can be lysed by human cytotoxic T lymphocytes.« less
  • Activation in lectin-free interleukin 2 (IL-2) containing supernatants of peripheral blood mononuclear leukocytes (PBL) from cancer patients or normal individuals resulted in expression of cytotoxicity toward 20 of 21 natural killer (NK)-resistant fresh solid tumor cells tested. Fresh solid tumor cells were resistant to NK-mediated lysis in 10 autologous patients' PBL-tumor interactions, and from 17 normal individuals tested against 13 allogeneic fresh tumors. Culture of PBL in IL-2 for 2-3 d was required for the lymphokine activated killers (LAK) to be expressed, and lytic activity toward a variety of NK-resistant fresh and cultured tumor targets developed in parallel. Autologous IL-2more » was functional in LAK activation, as well as interferon-depleted IL-2 preparations. Irradiation of responder PBL before culture in IL-2 prevented LAK development. Precursors of LAK were present in PBL depleted of adherent cells and in NK-void thoracic duct lymphocytes, suggesting that the precursor is neither a monocyte nor an NK cell. LAK effectors expressed the serologically defined T cell markers of OKT.3, Leu-1, and 4F2, but did not express the monocyte/NK marker OKM-1. Lysis of autologous fresh solid tumors by LAK from cancer patients' PBL was demonstrated in 85% of the patient-fresh tumor combinations. Our data present evidence that the LAK system is a phenomenon distinct from either NK or CTL systems that probably accounts for a large number of reported nonclassical cytotoxicities. The biological role of LAK cells is not yet known, although it is suggested that these cells may be functional in immune surveillance against human solid tumors.« less
  • We have previously reported that murine splenocytes incubated in the lymphokine interleukin-2 acquire the ability to mediate the lysis of a variety of fresh tumor cells in short-term chromium-51 release assays. This study was designed to evaluate the effect of lymphokine-activated killer (LAK) cells on fresh normal murine tissues. The susceptibility to lysis by LAK cells of single cell suspensions from a variety of murine tissues including lung, kidney, bone marrow, peripheral blood mononuclear cells, intestinal mucosa, liver, and fetus was studied. While kidney, intestinal mucosa, and peripheral blood mononuclear cells were clearly not lysed, there was a very lowmore » level of lysis of lung, bone marrow, liver, and fetus in repeated experiments. Separation of the cell suspensions of lung and bone marrow demonstrated much higher lysis of the adherent cell population, corresponding to an increased number of macrophages in the target cell suspension. Macrophages represent a population of cells particularly sensitive to lysis by LAK cells. All of the normal tissues were highly lysable by LAK cells in antibody-dependent cellular cytotoxicity assays in the presence of the appropriate anti-H-2 antibody. In a series of cold target inhibition studies, fresh normal murine kidney, lung, and bone marrow did not inhibit the lysis of the LAK-sensitive tumor target MCA-102, further demonstrating that fresh normal tissues share little if any of the determinant recognized by LAK cells on tumor targets. However, the MCA-105 and MCA-106 tumors, and the YAC cell line, all of which are sensitive to LAK cell lysis, did inhibit the lysis of MCA-102 tumor. These studies suggest that a common determinant is present on LAK-sensitive tissues that is absent or present in very low amounts on fresh normal tissues.« less
  • The effect of alcohol consumption on natural killer (NK) cell activity is controversial as both increased and decreased levels have been reported. It was the purpose of this study to determine the effects of feeding BDF1 mice different levels of alcohol on NK and lymphokine activated killer (LAK) cell activity. After four-six weeks of chronic alcohol feeding, mice were sacrificed, spleen cells obtained and assayed for NK and IL-2 boosted NK activity against YAC-1 cells in a traditional {sup 51}chromium release assay. Cells were also cultured in the presence of IL-2 for five days and tested for cytolytic activity usingmore » P815 cells as targets. Cells from each group were passed over a nylon wool column and the adherent (AD) and nonadherent (NAD) populations collected and tested as above. Increased NK, 24 hour IL-2 boosted NK and 5 day LAK activity were observed only in the spleen cells obtained from mice on 20% alcohol. Also, NAD populations had a 2-4 fold higher lytic unit values (LU{sub 20}) at all levels of alcohol consumption and in all assays, as compared with the unseparated spleen cells. Analysis of cell surface markers on these three populations of cells show that there were differences in MAC-2, Asialo GM-1, Thy 1.2, B220 and NK 1.1 that may correlate with the differences observed in the cytolytic assays. These data suggest that different levels of alcohol affect the cytolytic activity of NK and LAK cells and may result from alterations in the cell subset populations.« less