Biomedical subjects

B F Haynes

Publications and source records attributed to B F Haynes.

At least 145 records · Page 8Linked to original sources

PubMed1989

Immature human thymocytes can be driven to differentiate into nonlymphoid lineages by cytokines from thymic epithelial cells.

The signals and cellular interactions required for hematopoietic stem-cell commitment to the T lineage are unknown, yet are central to understanding the early stages of normal T-cell development. To study the differentiative capacity of T-cell precursors, we isolated CD4-, CD8-, surface(s) CD3- thymocytes from postnatal human thymuses and determined their capacity to differentiate into lymphoid and nonlymphoid lineages in vitro. We found that CD4-, CD8-, sCD3- thymocytes, which differentiated in the presence of T-cell conditioned medium plus interleukin 2 into T cells expressing the gamma delta receptor for antigen, were capable of differentiating into myeloid or erythroid lineages in the presence of either 5637 bladder carcinoma cell line conditioned medium plus recombinant human erythropoietin or human thymic epithelial cell conditioned medium. Thymic epithelial cell conditioned medium was as effective as 5637 supernatant plus erythropoietin in inducing myeloerythroid differentiation in the CD4-, CD8-, sCD3- thymocytes. Sixty-eight +/- 14% of CD4-, CD8-, sCD3- thymocytes underwent nonlymphoid differentiation within 4 days in culture with 5637 supernatant plus erythropoietin. Twenty-six +/- 4% of freshly isolated CD4-, CD8-, sCD3- cells were CD34+, and clonal granulocyte/macrophage, granulocyte/erythrocyte/monocyte/megakaryocyte, and T-cell progenitors were found in both CD34+ and CD34- subsets of CD4-, CD8-, sCD3- thymocytes. Thus, cells within the human CD4-, CD8-, sCD3- thymocyte subset can give rise to gamma delta+ T cells as well as to cells of myeloerythroid lineages. Moreover, CD34+, CD4-, CD8-, sCD3- cells can give rise to clonal T-cell progenitors as well as to clonal myeloid progenitors.

Antibodies, Monoclonal↗

PubMed1989

The gene SCL is expressed during early hematopoiesis and encodes a differentiation-related DNA-binding motif.

We have identified the human gene, SCL. We discovered this gene because of its involvement in a chromosomal translocation associated with the occurrence of a stem cell leukemia manifesting myeloid and lymphoid differentiation capabilities. Here we report the sequence of a cDNA for the normal SCL transcript, as well as for an aberrant fusion transcript produced in the leukemic cells. Although different at their 3' untranslated regions, both cDNAs predict a protein with primary amino acid sequence homology to the previously described amphipathic helix-loop-helix DNA binding and dimerization motif of the Ly1-1, myc, MyoD, immunoglobulin enhancer binding, daughterless, and achaete-scute families of genes. For these cDNAs, at least two different 5' ends are predicted, both of which retain this putative DNA binding domain and predict proteins in the range of 20-30 kDa. SCL mRNA is observed in "early" hematopoietic tissues. Taken together, these studies lead to the speculation that SCL plays a role in differentiation and/or commitment events during hematopoiesis.

Amino Acid Sequence↗

PubMed1989

Chromosomal translocation in a human leukemic stem-cell line disrupts the T-cell antigen receptor delta-chain diversity region and results in a previously unreported fusion transcript.

We have studied a leukemic stem-cell line, DU.528, that is able to differentiate into myeloid and lymphoid cells. The leukemic cells have a translocation between chromosomes 1 and 14, t(1;14)(p33;q11), which we have molecularly cloned and sequenced. Initial screening used joining (J)-segment probes from the T-cell receptor (TCR) alpha- and delta-chain loci. In apparent concert with the translocation, a deletion has occurred between delta-chain diversity (D)-region genes D delta 1 and D delta 2. D delta 2 was observed on derivative chromosome 1 [der(1)] and D delta 1 on der(14) with a deletion of the intervening 10 kilobases of germ-line DNA. The nature of the D delta 1-D delta 2 deletional event implicates a lymphoid recombinase in the mechanism of the translocation. As a consequence of the translocation, an unusual fusion transcript was generated. Probes from chromosome 1 detected a previously unreported transcript in RNA from both the cell line and the patient. A chromosome 14 probe identified the same transcript, thus confirming a fusion transcript derived from both chromosomes 1 and 14. This translocation may identify a gene for which we propose the name SCL (stem-cell leukemia) that is important for hemopoietic development and oncogenesis and that has been disrupted or altered in this stem-cell line.

Amino Acid Sequence↗

PubMed1989

Removal of fibroblasts from human epithelial cell cultures with use of a complement fixing monoclonal antibody reactive with human fibroblasts and monocytes/macrophages.

A complement fixing IgM monoclonal antibody (1B10) that reacts with surface membrane molecules of human fibroblasts, tissue macrophages, and peripheral monocytes was produced. In Western blot analysis of detergent extracts of cultured human foreskin fibroblasts, antibody 1B10 detected protein bands of Mr 43,000 and 72-80,000. We used the 1B10 antibody with complement to eliminate most 1B10 positive nonepithelial cells from thymic epithelial (TE) cell cultures, thereby allowing us to grow highly enriched populations of human TE cells.

Antibodies, Monoclonal↗

PubMed1989

CD7+, CD4-, CD8- acute leukemia: a syndrome of malignant pluripotent lymphohematopoietic cells.

Following our initial observation of in vivo conversion of CD7+, CD4-, CD8- acute lymphoblastic leukemia (ALL) cells from lymphoid to myeloid lineages (Proc Natl Acad Sci (USA) 81:253, 1984) we have studied eight additional cases of ALL with this leukemic cell phenotype. The CD7+, CD4-, CD8- phenotype was associated with a distinct clinical entity with those affected predominantly male (either less than 35 years or greater than 65 years of age), with frequent mediastinal and/or thymic masses, skin and CNS disease, high peripheral WBC counts, and bone marrow blasts that were morphologically L1 or not ascribable to a specific lineage. These patients did not respond to conventional chemotherapeutic regimens for either acute lymphoid or myeloid leukemias. No common karyotype or T-cell gene rearrangement pattern could be defined. Importantly, seven of eight patient's leukemic cells studied were capable of multilineage (myeloid, erythroid, monocytoid, megakaryocytoid, and lymphoid) differentiation in vitro. Data is presented suggesting that CD7+, CD4-, CD8- leukemias, in many instances, are leukemias of immature hematopoietic cells. The development of novel therapeutic approaches to this form of leukemia will be necessary to alter its poor prognosis.

Adolescent↗

PubMed1988

Analysis of expression of CD2, CD3, and T cell antigen receptor molecules during early human fetal thymic development.

To define early stages of T cell maturation during human fetal thymic development, we have used mAb reactive with CD2, CD3, and TCR molecules in indirect immunofluorescence assays on a series of early human fetal thymic specimens. Using a technique of quantitating the relative proportions of fluorescent-positive cells present in tissue sections, we found at 8.5 wk of gestational age after arrival of CD7+ T cell precursors into the thymic rudiment, 60% of thymic CD7+ cells were CD2+, 4% were CD3+ and none was TCR-delta+ or TCR beta+. Moreover, cells reactive with anti-CD2 antibodies against T11(2) and T11(3) epitopes of CD2 as well as thymic stromal cells expressing the CD2 ligand, lymphocyte function associated Ag-3, were also present at 8.5 wk. From 9.5 wk to birth TCR beta+ cells increased to include greater than 90% of all CD7+ cells while TCR-delta+ cells fell from a peak of 11% of CD7+ cells at 9.5 wk to 1% of CD7+ cells at birth. These data suggest that epitopes of CD2 molecules are expressed early on during fetal thymic development. Moreover, these data suggest that CD7+, CD2+, cytoplasmic CD3+ T cell precursors in man give rise to both TCR-delta+ T cells as well as to T cells expressing TCR-alpha beta.

Antibodies, Monoclonal↗

PubMed1988

Purified lymphocyte function-associated antigen-3 (LFA-3) activates human thymocytes via the CD2 pathway.

Defining the cellular and molecular mechanisms of interaction of developing thymocytes with nonlymphoid cells of the thymic microenvironment is critical for understanding normal thymus function. We have previously shown that the CD2/LFA-3 adhesion pathway is important in the interaction of thymocytes with a variety of LFA-3+ nonlymphoid thymic microenvironment cell types. Moreover, T cell activation via the CD2 (alternative, Ag independent) pathway is considered an important mechanism for intrathymic T cell proliferation. To study the relevance of CD2/LFA-3 interactions to human thymocyte activation, we have used purified LFA-3 Ag in several in vitro assays of thymocyte proliferation. Whereas LFA-3 Ag alone did not induce thymocyte proliferation, LFA-3 Ag in combination with the anti-CD2 antibody, CD2.1, and rIL-2 induced marked thymocyte proliferation. Additionally, the anti-CD28 antibody, Kolt2, could substitute for rIL-2, resulting in thymocyte activation induced by LFA-3 Ag in combination with antibodies CD2.1 and Kolt2. In both triggering systems, LFA-3 induced thymocyte activation was dependent upon the concentration of LFA-3 Ag. LFA-3 Ag-dependent thymocyte activation was directed primarily toward CD1-, mature thymocytes. Finally, intact SRBC that express the sheep homolog of LFA-3, T11TS, in combination with antibody CD2.1 and rIL-2 could also induce thymocyte activation. These data suggest that interaction of LFA-3 molecules with thymocyte CD2 molecules may provide a component of the stimulus for normal intrathymic thymocyte activation leading to thymocyte proliferation.

Animals↗

PubMed1988

A novel activation pathway for mature thymocytes. Costimulation of CD2 (T,p50) and CD28 (T,p44) induces autocrine interleukin 2/interleukin 2 receptor-mediated cell proliferation.

Prior studies have shown that thymocytes, unlike peripheral T cells, do not proliferate in response to mitogenic combinations of anti-CD2 mAbs. The present study demonstrated that stimulation by a mitogenic anti-CD2 combination (9-1 plus 9.6) with anti-CD28 induced vigorous thymocyte proliferation in the absence of exogenous IL-2. This thymocyte proliferation was IL-2 dependent as shown by the complete inhibition using anti-IL-2-R mAbs. Induction of IL-2-R transcripts was detected in thymocytes stimulated by the anti-CD2 antibody combination alone or the anti-CD2 combination plus anti-CD28 antibody. However, induction of IL-2 transcripts was observed only in thymocytes triggered jointly by the anti-CD2 combination plus anti-CD28 antibodies. The double-negative (CD4-8-) or CD1+ thymocytes isolated by sorting or by panning were unresponsive to CD2/CD28 triggering. The same mitogenic signal could induce vigorous proliferation of thymocytes with a mature phenotype, i.e., CD3+CD4+ or CD3+CD8+ thymocytes. Immunofluorescence studies demonstrated that the majority of CD3+ thymocytes were CD28+, and most of the CD28+ cells were located in the medullary compartment of thymus. These results indicated that the T cell lineage surface molecules CD28 and CD2 are involved in the regulation of expansion and further differentiation of mature thymocytes.

Antibodies, Monoclonal↗

PubMed1988

Early events in human T cell ontogeny. Phenotypic characterization and immunohistologic localization of T cell precursors in early human fetal tissues.

During early fetal development, T cell precursors home from fetal yolk sac and liver to the epithelial thymic rudiment. From cells that initially colonize the thymus arise mature T cells that populate T cell zones of the peripheral lymphoid system. Whereas colonization of the thymus occurs late in the final third of gestation in the mouse, in birds and humans the thymus is colonized by hematopoietic stem cell precursors during the first third of gestation. Using a large series of early human fetal tissues and a panel of monoclonal antibodies that includes markers of early T cells (CD7, CD45), we have studied the immunohistologic location and differentiation capacity of CD45+, CD7+ cells in human fetal tissues. We found that before T cell precursor colonization of the thymus (7-8 wk of gestation), CD7+ cells were present in yolk sac, neck, upper thorax, and fetal liver, and were concentrated in mesenchyme throughout the upper thorax and neck areas. By 9.5 wk of gestation, CD7+ cells were no longer present in upper thorax mesenchyme but rather were localized in the lymphoid thymus and scattered throughout fetal liver. CD7+, CD2-, CD3-, CD8-, CD4-, WT31- cells in thorax and fetal liver, when stimulated for 10-15 d with T cell-conditioned media and rIL-2, expressed CD2, CD3, CD4, CD8, and WT31 markers of the T cell lineage. Moreover, CD7+ cells isolated from fetal liver contained all cells in this tissue capable of forming CFU-T colonies in vitro. These data demonstrate that T cell precursors in early human fetal tissues can be identified using a mAb against the CD7 antigen. Moreover, the localization of CD7+ T cell precursors to fetal upper thorax and neck areas at 7-8.5 wk of fetal gestation provides strong evidence for a developmentally regulated period in man in which T cell precursors migrate to the epithelial thymic rudiment.

Antigens, CD7↗

PubMed1988

Human thymic epithelial cells produce granulocyte and macrophage colony-stimulating factors.

The development of culture conditions for growing normal human thymic epithelial (TE) cells free from contamination with other stromal cells has allowed us to identify and characterize TE cell-derived cytokines. In this study, we report that cultured human TE cells produced CSF that supported the growth of clonal hematopoietic progenitor cells in the light density fraction of human bone marrow cells. Thymic epithelial supernatants (TES) induced growth of granulocyte/macrophage colonies (CFU-GM), mixed granulocyte/erythrocyte/monocyte/megakaryocyte colonies (CFU-GEMM), and early burst-forming unit erythroid colonies (BFU-E). In addition, TES induced differentiation of the promyelocyte leukemic cell line HL-60 and stimulated growth of both granulocyte (CFU-G) and monocyte (CFU-M) colonies from murine bone marrow cells. Using anion exchange column chromatography, pluripotent CSF activities in TES were separated and shown to be distinct from an IL-1-like cytokine that has been shown as a TE cell-derived cytokine (TE-IL-1). Colony-stimulating activity supporting the growth of bone marrow CFU-GEMM, BFU-E, and CFU-GM co-eluted at 150 to 180 mM NaCl. A separate peak of CFU-GM-stimulating activity eluted early in the gradient at 20 mM NaCl. In Northern blot analysis of enriched RNA, synthetic oligonucleotide probes complementary to human G-CSF and M-CSF coding sequence each hybridized with a single RNA species of 1.7 and 4.4 kb, respectively. These data suggest that normal human TE cells synthesize G-CSF and M-CSF that promote differentiation of non-lymphoid hematopoietic cell precursors.

Animals↗

PubMed1988

Synovial microenvironment-T cell interactions. Human T cells bind to fibroblast-like synovial cells in vitro.

Synovitis in rheumatoid arthritis is characterized by infiltration of the synovium by T and B lymphocytes and monocytes, as well as by the proliferation of synovial lining cells, fibroblasts, and endothelial cells. To study synovial cell-T cell interactions in vitro, we established cultures of fibroblast-like synovial cells, and used these cells in a synovial cell-T cell binding assay. Using T cells at various stages of differentiation and activation, we found that human thymocytes and mitogen-activated peripheral blood T cells bound to fibroblast-like synovial cells, whereas fresh peripheral blood T cells did not. Moreover, activated T cells from inflammatory synovial tissue or from synovial fluid also bound to fibroblast-like synovial cells cultured in vivo. Antibodies against certain epitopes of the T cell CD2 (35.1) and synovial cell lymphocyte function-associated antigen-3 (LFA-3) (TS2/9) molecules inhibited synovial cell-thymocyte binding. However, these same anti-CD2 and anti-LFA-3 antibodies only partially inhibited synovial cell binding to activated normal peripheral blood T cells. Moreover, T cells from inflammatory synovium from rheumatoid arthritis and psoriatic arthritis patients also bound to synovial cells in vitro. These findings demonstrate that fibroblast-like synovial cells are capable of binding to human T cells in vitro, and suggest that during the course of inflammatory synovitis, synovial fibroblast-T cell interactions may occur in vivo.

Antigens, Differentiation↗

PubMed1988

Human T-cell lymphotropic virus I and adult T-cell leukemia: report of a cluster in North Carolina.

PURPOSE: Human adult T-cell leukemia-lymphoma is a malignant, proliferative disease of CD4+ lymphocytes associated with infection with human T-cell lymphotropic virus type I (HTLV-I). Following the presentation of a patient who was infected with the virus, we undertook a study of his family members and sexual contacts to see if a cluster of infected persons could be identified. CASE REPORT: A black heterosexual North Carolina native with a history of drug abuse presented with jaundice, and pancytopenia subsequently developed. He then became hypercalcemic and leukemic, with high numbers of circulating, morphologically abnormal CD4+ lymphocytes. RESULTS: As determined by radioimmunoassay and immunoblot analyses, the serum of the index case contained antibodies against core proteins (p19 and p24) of HTLV-I. When cultured in vitro with interleukin-2, the lymphocytes expressed HTLV-I specific core proteins. The virus recovered from these T cells was transmitted to cord blood T cells, which became immortalized for continuous growth in vitro, expressed HTLV-I p19 protein, and displayed characteristic C-type particles by electron microscopy. Studies of family members and sexual contacts, all of whom were black, heterosexual central North Carolina natives, revealed five of 28 whose serum had anti-HTLV-I antibodies as determined by radioimmunoassay and immunoblot. Neither the patient nor the seropositive family/contacts had antibodies against human immunodeficiency virus proteins. Four of the six people with HTLV-I infection had no history of intravenous drug abuse. Three of the five seropositive family/contacts had circulating, morphologically abnormal lymphocytes suggestive of "preleukemic" or "smoldering" human adult T-cell leukemia-lymphoma.

Adult↗

PubMed1988

Type-specific neutralization of the human immunodeficiency virus with antibodies to env-encoded synthetic peptides.

A synthetic peptide (SP-10-IIIB) with an amino acid sequence [Cys-Thr-Arg-Pro-Asn-Asn-Asn-Thr-Arg-Lys-Ser-Ile-Arg-Ile-Gln-Arg-Gly-Pro -Pro-Gly-(Tyr); amino acids 303-321] from the human immunodeficiency virus (HIV) isolate human T-cell lymphotropic virus type III (HTLV-III) HTLV-IIIB envelope glycoprotein gp120 was coupled to tetanus toxoid and used to raise goat antibodies to HIV gp120. Goat anti-SP-10-IIIB serum bound to the surface of HTLV-IIIB-infected CEM T cells but not to the surface of HTLV-IIIRF-infected or uninfected CEM T cells. Anti-SP-10-IIIB antibodies also selectively bound to gp120 from lysates of HTLV-IIIB cells in immunoblot assays. Twenty-one percent of sera (28 of 175) from patients seropositive for HIV contained antibodies that reacted with SP-10-IIIB in RIA. Human anti-SP-10-IIIB antibodies affinity purified from acquired immunodeficiency syndrome (AIDS) patient serum bound to HTLV-IIIB-infected cells and immunoprecipitated gp120. Goat antibodies to SP-10-IIIB neutralized HTLV-IIIB (80% neutralization titer of 1/600), inhibited HTLV-IIIB-induced syncytium formation, but did not neutralize HIV isolates HTLV-IIIRF or HTLV-IIIMN or inhibit syncytium formation with these isolates. Also, goat antiserum to an homologous synthetic peptide [SP-10-IIIRF(A), (Cys)-Arg-Lys-Ser-Ile-Thr-Lys-Gly-Pro-Gly-Arg-Val-Ile-Tyr] from gp120 of HIV isolate HTLV-IIIRF inhibited syncytium formation by HTLV-IIIRF, but did not inhibit syncytium formation by HTLV-IIIB or by HTLV-IIIMN. Thus, the amino acid sequences of SP-10-IIIB and SP-10-IIIRF(A) define homologous regions of gp120 that are important in type-specific virus neutralization. The identification of these type-specific neutralizing epitopes should facilitate the design of a polyvalent, synthetic vaccine for AIDS.

Acquired Immunodeficiency Syndrome↗

PubMed1988

Human thymic epithelial cells directly induce activation of autologous immature thymocytes.

To study the role that epithelial cells of the thymic microenvironment play in promoting activation of immature CD7+, CD2+, CD4-, CD8- (double-negative) human thymocytes, we have isolated thymocyte subsets from normal postnatal thymus and have cocultured autologous double-negative thymocytes with pure populations of thymic epithelial (TE) cells. We report that TE cells directly activate double-negative thymocytes to proliferate and that TE cells enhance the ability of double-negative thymocytes to proliferate in response to stimulation with exogenous interleukin 2. Activated double-negative thymocytes that proliferated in vitro in the presence of TE cells and interleukin 2 remained double-negative after 23 days in culture. Moreover, TE-cell culture supernatants in the absence of intact TE cells contain interleukin 1, interleukin 3, and granulocyte/macrophage-colony-stimulating factor activity for human bone marrow cells and can activate double-negative thymocytes to proliferate. Antibodies against interleukin 1 and against granulocyte/macrophage-colony-stimulating factor inhibited TE-cell-induced thymocyte activation. These data indicate that one role of TE cells in vivo may be to activate double-negative thymocytes to proliferate.

Antigens, Differentiation, T-Lymphocyte↗

PubMed1988

Demonstration of phenotypic abnormalities of thymic epithelium in thymoma including two cases with abundant Langerhans cells.

A panel of monoclonal antibodies that phenotypically define stages of normal human thymic epithelial (TE) cell maturation was used to compare thymic epithelium of nine thymomas with hyperplastic thymic epithelium in myasthenia gravis (MG) and thymic epithelium of normal thymuses. It has been shown previously that normal thymic epithelial cells express antigens of early TE cell maturation (A2B5, TE-4) throughout thymic ontogeny and acquire antigens 12/1-2, TE8, and TE-15 at 14 to 16 weeks of fetal gestation. Hyperplastic MG thymic epithelial cells expressed TE antigens in phenotypic patterns similar to that seen in normal postnatal thymus, ie, TE in subcapsular cortex and medulla was TE4+, A2B5+, and 12/1 - 2+ and Hassall's bodies were reactive with antibodies TE8 and TE15. In contrast, thymic epithelium in primary mediastinal thymomas was TE4+, A2B5+, TE8-, and greater than 75% of thymoma epithelium was 12/1 - 2-, a thymic epithelial phenotype similar to that seen on normal fetal thymic epithelium at 14 to 16 weeks fetal gestation. In one subject with a mature epithelial histologic pattern, thymoma epithelium was found to be strongly TE8+, a phenotype suggestive of a later stage of TE maturation. Lymphocytes in five of seven thymomas with immature thymic epithelial cells predominantly expressed immature thymocyte phenotype while two thymomas with immature epithelial phenotype showed a predominance of Langerhans cells and surrounding lymphocytes expressing a mature phenotype. Lymphocytes in the thymoma with differentiated epithelial cells expressed a mature thymocyte phenotype. Thus, in thymomas of varying histologic types, phenotypic abnormalities of thymic epithelium are present; these phenotypic abnormalities may reflect abnormal thymic epithelial maturation.

Adult↗

PubMed1988

Differentiation of human T cells.

This article discusses the ontogeny of human T cells along with the relationship of normal T-cell maturation to the development of various malignant T-cell syndromes. The impact of monoclonal antibody technology, the discovery of the T-cell receptor for antigen, and the discovery of mechanisms of thymocyte-thymic microenvironment interactions on the analysis of human T-cell development are emphasized.

Antibodies, Monoclonal↗

PubMed1987

Monoclonal antibodies to CD2 and lymphocyte function-associated antigen 3 inhibit human thymic epithelial cell-dependent mature thymocyte activation.

Recent study of human thymocyte-thymic epithelial (TE) cell interactions has demonstrated that thymocytes bind to TE cells, and a consequence of this binding is the provision of accessory cell signals by TE cells for phytohemagglutinin (PHA)-induced mature thymocyte activation. In this paper we report on studies of the molecules involved in TE cell-dependent mature thymocyte activation. TE-thymocyte interactions necessary for PHA-induced thymocyte activation were inhibited by monoclonal antibodies against the cluster of differentiation (CD)2 antigen on thymocytes and lymphocyte function-associated (LFA)-3 antigen on TE cells. Inhibition of TE accessory cell signals by antibodies against CD2 (alpha CD2) and LFA-3 (alpha LFA-3) antigens occurred early on during thymocyte activation and prevented thymocyte interleukin 2 receptor expression. Further, alpha CD2 and alpha LFA-3 inhibited PHA-induced thymocyte activation in whole thymic explant cultures suggesting a significant role of the CD2 and LFA-3 antigens in thymocyte activation when accessory cell signals for PHA-induced thymocyte triggering were delivered by cells within an intact thymic microenvironment.

Antibodies, Monoclonal↗

PubMed1987

Combined chemoseparation and immunoseparation of clonogenic T lymphoma cells from human bone marrow using 2'-deoxycoformycin, deoxyadenosine, 3A1 monoclonal antibody, and complement.

Chemoseparation and immunoseparation techniques have been combined to eliminate malignant clonogenic T lymphoma cells from human bone marrow. Incubation with 5 microM 2'-deoxycoformycin and 500 microM deoxyadenosine has eliminated 2 logs of HSB-2 T lymphoma cells from a 20-fold excess of irradiated human bone marrow. Multiple incubations with 3A1 antibody and rabbit complement eliminated approximately 2 logs of HSB-2 cells from similar mixtures. Used in combination, the 2 techniques eliminated up to 4 logs of T lymphoma cells. Incubation of normal human bone marrow under similar conditions failed to affect growth of granulocyte-macrophage colony-forming cell units, burst-forming erythroid units, or multipotential erythroid-granulocyte-megakaryocyte-macrophage colony-forming hematopoietic progenitor cells units.

Antibodies, Monoclonal↗