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R L Truitt

Publications and source records attributed to R L Truitt.

At least 55 records · Page 3Linked to original sources
PubMed1984

Migration patterns and functional activity of cloned cytotoxic T lymphocytes in syngeneic and allogeneic mice.

The quantitative distribution of cytolytic T lymphocytes (CTL) generated in mixed leukocyte culture (MLC) and an interleukin-2 (IL-2)-dependent, CTL clone (WRL-A3) was investigated in various tissues of irradiated syngeneic and allogeneic mice. In addition, the ability of the WRL-A3 CTL clone to remain viable and retain antigen specificity following in vivo passage was evaluated. Injection i.v. of 51Cr-labeled cultured CTL resulted in: (1) extensive deposition of cells in the lungs with significantly more lymphocytes being recovered in allogeneic as compared with syngeneic lung tissue; (2) minimal accumulation in spleen with more in syngeneic than in allogeneic tissue; and (3) no localization in blood, femurs, thymus, or lymph nodes. The migration rate of cultured CTL exiting the lung during the first 4 hr was markedly faster in syngeneic than in allogeneic recipients and was directly associated with the distribution of these cells in other tissues at 24 hr. The WRL-A3 CTL clone recovered from irradiated syngeneic and allogeneic lung tissue at 1, 3, 6, 8, and 13 days after i.v. injection remained viable, even though no exogenous IL-2 was administered to the recipient mice. The recovered cells proliferated when recultured with IL-2, and retained their antigen specificity for Qed-1b target cells after in vivo passage. These findings indicate that restricted and undesirable tissue distribution, rather than impaired viability or loss of antigenic specificity, is the major obstacle to successful use of cultured CTL for adoptive immunotherapy of disseminated cancer.

Animals↗
PubMed1983

Growth of AKR T cell leukemia lymphoblasts in medium containing interleukin 2 (IL-2).

Long-term cloned mouse leukemic T cell lines were established in vitro using interleukin-2 (IL-2) conditioned media. The cell lines were tested for retention of both antigenic expression and tumorigenicity, as well as for growth characteristics. Several important findings resulted from these studies. A reliable method was developed for consistent success in the culturing and cloning of leukemic T cell lines. Cultured cells from IL-2-dependent lines were found to retain their original histocompatibility and differentiation antigen characteristics for up to 2 yr. Mortality patterns, comparing long-term cloned leukemic T cell lines with fresh AKR leukemia cells, showed that the cloned cells had greater tumorigenicity. An especially interesting finding was that cell lines established both from different mice and from a single organ of an individual mouse were heterogeneous with respect to antigenic makeup, cell growth kinetics, and tumorigenicity. Finally, because of their dependence on IL-2, the cloned tumor cell lines provided excellent index cells to quantify IL-2 activity.

Animals↗
PubMed1983

Characterization of alloimmunization-induced T lymphocytes reactive against AKR leukemia in vitro and correlation with graft-vs-leukemia activity in vivo.

We have reported that immunization of H-2k mice with lymphoid cells from various allogeneic strains induced a population of cells that could eliminate first-passage spontaneous AKR leukemia from the spleens of immuno-suppressed AKR (H-2k) hosts. In the present study, we examined the nature of the cells responsible for this graft-vs-leukemia (GVL) reaction and compared them to cytolytic cells detected in vitro. Spleen cells from alloimmunized CBA/J (H-2k) mice were selectively depleted of various subpopulations by treatment with antibody and complement (C), then tested in vivo for GVL reactivity. Cell suspensions depleted of Thy-1.2+, Lyt-1+, or Lyt-2+ lymphocytes had no significant GVL reactivity, whereas suspensions depleted of NK-1.2+ cells retained GVL reactivity. The GVL-reactive cells persisted in H-2-compatible donor mice for up to 56 days. Lyt-1+2+ lymphocytes that were cytotoxic for cultured AKR leukemia cells in vitro could be detected in the spleens of alloimmunized H-2-compatible mice after expansion of the cells in T cell growth factor. Using quantitative limiting dilution cytotoxicity assays, we found that the frequency of leukemia-reactive cytotoxic lymphocytes (CL) in the spleen showed a direct correlation with the GVL efficacy of the cells in vivo. Alloimmunization was essential for induction of the GVL-reactive cell population. CL in alloimmunized mice consisted of heterogeneous cytotoxic specificities; i.e., some CL were leukemia-specific, others lysed only nonleukemic AKR target cells, and a third group mediated killing of both leukemic and nonleukemic target cells. The CL appeared to be H-2 restricted and specific for non-H-2 antigens shared by the AKR leukemia and the alloimmunizing cells.

Animals↗
PubMed1980

Alloimmunization: induction of antileukemic reactivity without modification of anti-host reactivity in H-2-compatible mice.

Transplanted immunocompetent cells from CBA (H-2k) mice immunized against individual or pooled lymphoid cells from various allogeneic strains resulted in the elimination of widely disseminated leukemia cells in AKR (H-2k) host mice as measured in a GVL bioassay. In most cases, alloimmunization resulted in reactivity against AKR-L comparable to that observed when CBA donors were specifically immunized with irradiated AKR-L cells. Cells from unimmunized or isoimmunized CBA mice had no detectable GVL reactivity. Alloimmunization caused no increase in the mild GVH reactivity of unimmunized or isoimmunized CBA lymphoid cells transplanted into lethally irradiated nonleukemic AKR hosts; whereas, specific immunization with AKR-LX cells resulted in significantly increased GVH-related mortality.

AKR murine leukemia virus↗
PubMed1978

Graft versus leukemia. VIII. Selective reduction in antihost reactivity without loss of antileukemic reactivity by treatment of donor mice with lipopolysaccharide.

Spleen and lymph node cells from DBA/2 (H-2d) donor mice treated with multiple injections of bacterial lipopolysaccharide (LPS) were tested in vivo for reactivity against normal tissues of host AKR (H-2k) mice against an AKR long-passage, acute lymphoblastic leukemia (BW5147). LPS treatment of donor mice resulted in a reduction in graft-versus-host (GVH) reactivity without loss of graft-versus-leukemia (GVL) reactivity. Immunocompetent cells from LPS treated DBA/2 donors were effective when used for adoptive immunotherapy (in combination with chemoradiotherapy) of BW5147 leukemia. GVH associated mortality decreased as the dose of spleen cells from LPS treated histoincompatible donors was increased as much as four times the number necessary to eliminate leukemia. The mechanism by which LPS reduced GVH reactivity without eliminating GVL reactivity is unclear; however, it does not appear to be the result of a dilution in the number of GVH reactive cells by nonlymphoid elements in the donor spleen nor of the adjuvant effects of LPS on resistance to bacterial infections.

Animals↗
PubMed1977

Growth of human tumors in lethally irradiated mice reconstituted with syngeneic fetal liver cells.

Transplantation into lethally irradiated mice of hematopoietic and lymphoid cells from immature donors which hypothetically will not mount a cell mediated attack against simultaneously inoculated human tumor cells has resulted in tumor engraftment and growth in long-term surviving radiation chimeras. Twenty-four hours after lethal irradiation, A or CBA mice were given iv injections of 2 X 10(7) fetal liver cells from syngeneic donors of 14, 16, or 18 days of embryonation and sc injections of 1, 3, or 6 X 10(6) human choriocarcinoma (C-1, C-2, and C-3) cells or human breast carcinoma (B-1) cells that had been maintained in culture. Palpable tumors greater than or equal to 5 mm were noted in 18/22 mice injected with C-1, 9/16 with C-2, 10/10 with C-3, and 18/30 with B-1. Tumors of 17 (31%) of mice remained palpable until death of the animal or until termination of the experiment 100 days post inoculation. Histologic study of autopsy specimens revealed malignant tumors with occasional pulmonary metastases. Human chorionic gonadotropin was found in the serum of mice that received choriocarcinoma cells.

Animals↗
PubMed1977

AKR T-cell acute lymphoblastic leukemia: a model for human T-cell leukemia.

In humans, the T cell form of acute lymphoblastic leukemia has proved to be a difficult therapeutic challenge; long-term remissions are unusual. Spontaneous T cell leukemia of AKR mice bears many similarities to the human disease and is proposed as an experimental model in which to test treatment strategies prior to clinical trial.

Acute Disease↗
PubMed1976

Allogeneic bone marrow chimerism in germ-free mice. IV. Therapy of "Hodgkin's-like" reticulum cell sarcoma in SJL mice.

"Hodgkin's-like reticulum cell sarcoma develops spontaneously in most SJL mice. Germ-free and conventional SJL mice bearing advanced reticulum cell sarcoma were treated with X-irradiation and transplantation of bone marrow from SJL or C3H/He donors. The 120-day survival rate of germ-free mice receiving allogeneic bone marrow (70%) exceeded that of all control groups; more importantly, germ-free mice that survived more than 4 months after treatment with allogeneic cells had no evidence of neoplastic lesions when killed. The germ-free environment effectively prevented graft-versus-host disease that was lethal to conventional mice. The results of these experiments offer additional evidence that bone marrow transplantation can be used as a therapeutic tool for spontaneous murine neoplasms.

Animals↗
PubMed1976

Transplantation of hematopoietic and lymphoid cells in mice.

CBA mice were exposed to a supralethal dose of whole body X-irradiation and recieved transplants of graded, small doses of bone marrow, fetal liver, or fetal liver plus fetal thymus cells obtained from H-2 matched C58 or H-2 mismatched A donors. Survival at 20 days was used to evaluate the ability of the transplants to restore hematopoiesis following the acute radiation injury. In the higher dose ranges of 6 X 10(7) and 1.2 X 10(8) cells/kg body weight, the fetal cells were as effective as adult bone marrow in both the matched and mismatched strain combinations. Survival at 100 days was used to evaluate the severity of chronic graft-versus-host disease produced by each of the transplants. In the higher dose ranges, cells from fetal donors promoted higher long-term survival rates than did comparable doses of bone marrow cells in both the matched and mismatched strain combinations. In some experimental groups, the addition of fetal thymus cells to fetal liver cells resulted in higher short-term and long-term survival rates than did fetal liver alone, but this was inconsistent and generally fell short of statistical significance. The most important finding was that cells from mismatched unrelated fetal donors (using a cell dose per kilogram body weight comparable to the number of fetal liver and thymus cells which would be obtainable from one human fetus at 14 weeks of embryonation) promoted higher long-term survival rates than did bone marrow transplants from matched unrelated donors.

Animals↗
PubMed1976

Graft-versus-leukemia for AKR spontaneous leukemia-lymphoma.

Adoptive immunotherapy in the form of a transient graft of mismatched DBA/2 BM + LN cells was used in combination with several chemoradiotherapy regimens to treat AKR mice bearing advanced SLL. Leukemic mice treated in this manner had a significant prolongation of their MST and significantly higher survival rates 60 and 90 days posttreatment than corresponding control groups. Syngeneic- or allogeneic-matched cells did not provide substantial GVL effect. An inverse relationship that influenced survival was observed between the radiation dose and the dose of GVL effector cells used to treat leukemic AKR mice in the treatment model. Recurrence leukemia remains a major problem.

Amphotericin B↗
PubMed1976

Mitigation of graft-versus-host disease in mice by treatment of donors with bacterial endotoxin.

Treatment of DBA/2 (H-2d) mice with bacterial endotoxin prior to transplantation of their spleen and lymph node cells into immunosuppressed AKR (H-2k) mice prevented acute mortality from graft-versus-host (GVH) disease. AKR mice that received immunocompetent cells from untreated DBA/2 mice had a median survival time (MST) of 13 days. In contrast, AKR mice that received immunocompetent cells from endotoxin-treated DBA/2 donors had an MST of 54 days. Endotoxin treatment of AKR recipients was not essential for preventing mortality from acute GVH disease. Chimerism was proved by demonstrating that the lymphoid cells of long-term surviving AKR mice had the characteristics of DBA/2 lymphoid cells as measured by their response in mixed leukocyte culture (MLC) tests. Spleen cells from endotoxin-treated DBA/2 mice were able to stimulate, and to be stimulated by, AKR spleen cells in MLC assays. Furthermore, spleen cells from endotoxin-treated DBA/2 mice did not suppress the responses of DBA/2 or AKR spleen cells in 'three-party' MLC tests.

Animals↗
PubMed1975

Low-dose chemotherapy as a prelude to intensive treatment of spontaneous leukemia-lymphoma in AKR mice.

Groups of AKR mice bearing spontaneous leukemia-lymphoma were treated with five different combinations of chemotherapy or chemoradiotherapy. Each treatment combination was given in two sequences--high dose first and low dose last, or low dose first and high dose last--administered over 6-7 days. When the initial treatment was a high dose of chemotherapy, radiotherapy, or chemoradiotherapy, mortality in the first 24 hours exceeded 40%, and at least 70% of the mice in each group were dead within 2 weeks. When low-dose chemotherapy was given first, mortality in the first 24 hours was minimal but, most significantly, no deaths occurred in the 24 hours after subsequent high-dose treatment. In the most successful group (100 mg cyclophosphamide/kg on day 0, and 250 mg cyclophosphamide/kg and 400 R total-body X-irradiation on day 7), the median survival time increased significantly as compared with the median survival time among mice given the same regimen in reverse sequence (p less than 0.001) or among untreated control mice (p less than 0.01). With this regimen, survival 60 days after the last treatment was 47%. No mouse survived 30 days when the sequence of treatments was reversed. From these results, we conclude that chemotherapeutic and chemoradiotherapeutic regimens for AKR spontaneous leukemia-lymphoma should be designed so that low, minimally lethal doses precede higher doses.

Amphotericin B↗