Decreased suppressor T-lymphocytes in autoimmune thyroid diseases detected by monoclonal antibodies

Monoclonal antibodies reacting with cell surface antigens of helper (T4), suppressor (T8) T cells and common T-cell antigen (T3) were used by an immunofluorescence technique to enumerate peripheral T-lymphocytes in 42 patients with Graves' disease and 16 patients with Hashimoto's thyroiditis. The percentages of total T cells (cells which react with anti-T3) and helper/inducer cells (cells which react with anti-T4) among peripheral mononuclear cells in Graves' and Hashimoto's patients were not significantly different from those found in normal controls, except for a decrease in cells which react with anti-T3 in toxic Graves' disease without medication. The most important finding was a decrease in the percentage of cytotoxic/suppressor T cells (cells which react with anti-T8) in toxic Graves' disease and Hashimoto's thyroiditis. In patients with Graves' disease who were hyperthyroid or euthyroid on propylthiouracil treatment and euthyroid after radioactive iodide treatment, the percentage of cells which react with anti-T8 was also decreased, but this did not reach statistical significance. These findings support the hypothesis of defects in suppressor T-lymphocytes in autoimmune thyroid diseases.     

Activation of resting human B cells by helper T-cell clone supernatant: characterization of a human B-cell-activating factor.

The effects of helper T-cell clone supernatants on resting human B cells were investigated. Four different helper T-cell clones (two T4+ and two T8+) were stimulated by anti-T3 monoclonal antibodies on Sepharose beads or anti-T11(2) plus anti-T11(3) monoclonal antibodies. The supernatants from these activated clones induced the proliferation of highly purified resting B lymphocytes from the peripheral blood. The B cells exhibited a cell size and a surface-antigen pattern (4F2 antigen and transferrin receptor) of phase G0 B cells, and they were functionally resting. In response to T-cell supernatants a large fraction of the B cells enlarged and expressed 4F2 antigens and transferrin receptors. In gel filtration, the corresponding activity migrated with an apparent Mr of 12,000-15,000. Our findings strongly support the existence of a human B-cell-activating factor acting on resting B cells and causing them to enter phase G1 of the cell cycle.     

Surface phenotype of Japanese adult T-cell leukemia cells characterized by monoclonal antibodies

We studies the surface phenotype and the functional activities of leukemic cells from three patients with Japanese adult T-cell leukemic (ATL) using the panel of OK and anti-Tac monoclonal antibodies, which react with differentiation antigens and define functionally distinct T- cell subsets or activated and terminally differentiated T cells. The phenotype of ATL cells were determined to be OKT1+T3+T4+T10+T5-T8-Okla1- , although cells from two patients suppressed pokeweed mitogen (PWM) induced normal B-cell differentiation, and cells from all patients lacked helper activity in this system. In addition, after cultivation with PWM, ATL cells from all patients were reactive with anti-Tac monoclonal antibody, and cells from one patient were reactive with OKlal. These findings suggest that ATL cells arise from peripheral mature T-cell subsets and also suggest that the transition of surface phenotype of ATL cells to functionally mature and activated T cells occurs in culture.     

Proliferative responses of human intraepithelial lymphocytes to various T-cell stimuli

Human intraepithelial lymphocytes (IEL) are CD8+ T cells located between intestinal epithelial cells, capable of only minimal proliferation to mitogens but brisk proliferation to mitogens combined with sheep red blood cells. This study examines this differential response of IEL. Both IEL and CD8+ T lymphocytes from the peripheral blood are predominantly CD2+, CD3+, CD4-, CD5+, CD8+, and express the alpha beta subunits of the T-cell receptor. Human IEL express the same densities of the CD2, CD3, and CD8 antigens but a lower density of the CD5 antigen than do peripheral blood CD8+ T cells. The proliferation of IEL is significantly less than that of peripheral blood CD8+ T lymphocytes in response to phytohemagglutinin, to concanavalin A, or to anti-CD3 antibody bound to Sepharose (p less than 0.05). Supplementing IEL with interleukin-1, interleukin-2, or autologous peripheral blood macrophages does not completely reconstitute the proliferative response of IEL to these stimuli. Rather, the low proliferation of IEL to these stimuli is due to incomplete activation, as demonstrated by the low percentage of CD25 (Tac)+ lymphocytes with concanavalin A or the low density of the CD25 antigen with phytohemagglutinin. Both IEL and peripheral blood CD8+ T lymphocytes proliferate minimally in response to alloantigens or to interleukin-2, but briskly in response to stimuli of the CD2 receptor such as the combination of anti-T11(2) and anti-T11(3) antibodies or mitogen and sheep red blood cells. The sheep red blood cells enhance the mitogen-induced response of IEL by augmenting events of activation, both interleukin-2 production and interleukin-2 receptor expression. Thus, IEL represent an unusual compartment of CD2+, CD3+ T lymphocytes that are activated more completely by stimuli of the CD2 receptor than by stimuli of the CD3 receptor or by T-cell mitogens.     

Two separate functions of class II (Ia) molecules: T-cell stimulation and B-cell excitation.

We have evaluated the role of major histocompatibility complex-encoded class II (Ia) molecules as transmembrane signaling receptors in the T helper cell-dependent activation of B lymphocytes. For these studies, we utilized the murine B-cell lymphoma CH12, which expresses both I-A and I-E class II molecules. In addition, CH12 cells carry IgM of known antigen specificity and require both specific antigen and Ia-restricted T-cell help for the induction of antibody secretion. In this respect, they resemble normal resting B cells. We have studied the ability of antigen-specific or alloreactive T helper cells reactive with either the I-A or the I-E molecules on CH12 to be activated and their ability to stimulate antibody production by CH12. The results show that, although CH12 cells present antigen to T helper cells that interact with either the I-A or the I-E molecules, CH12 cells are stimulated to secrete antibody only by T helper cells reactive with their I-E molecules. Our data demonstrate that class II molecules are transducers of signals for B-cell excitation in addition to serving a restricting function for helper T-cell stimulation. Moreover, the data demonstrate that these two functions, T-cell stimulation and B-cell excitation, are discrete and need not be expressed by the same Ia molecule.     

A novel antigen detected by the CBF.78 antibody further distinguishes anaplastic large cell lymphoma from Hodgkin's disease

A novel antigen detected by the CBF.78 monoclonal antibody (MoAb) is strongly expressed on cortical thymocytes and weakly expressed on resting peripheral T lymphocytes. Expression of the antigen is increased on phytohemagglutinin (PHA)- and anti-CD3-activated T lymphocytes and on Epstein-Barr virus-transformed B lymphocytes. The CBF.78 immunoprecipitated a protein of 116 kD from resting and PHA- activated peripheral blood mononuclear cells. CBF.78 MoAb did not inhibit T-cell proliferation induced by anti-CD3 antibody. This MoAb was effective for immunostaining on paraffin sections after microwave- oven heating of tissue sections. Among malignant lymphomas, the antigen recognized by CBF.78 MoAb was found to be mainly expressed by T-cell lymphomas (49+ of 74), particularly those of high-grade malignancy (31+ of 36), whereas only occasional B-cell lymphomas (4+ of 107) expressed the antigen. A distinctive pattern of reactivity was shown by 108 cases of anaplastic large cell lymphomas. Strong positivity for CBF.78 antibody was observed in 86+ of 108 cases, irrespective of B, T, or null phenotype. This multicenter study suggests that CBF.78 MoAb could be of diagnostic value in differentiating Hodgkin's-like anaplastic large cell lymphomas from cases of Hodgkin's disease rich in neoplastic cells. Only a few cases of Hodgkin's disease (13+ of 126) showed rare Reed-Sternberg cells that stained, In these few cases, staining was weak to moderate and confined to cytoplasm. CBF.78 MoAb was nonreactive with all nonhematopoietic neoplasms examined (0+ of 48). Further studies should delineate the function of this new antigen and its clinical utility.     

Monoclonal antibody to human cytotoxic-suppressor T-lymphocytes cross-reacts with canine lymphocytes and inhibits cell-mediated lympholysis of canine cells

Of 19 murine antihuman Tp32 (T8) monoclonal antibodies tested, only antibody T811 showed cross-reactivity with canine lymphoid cells. It recognized an antigen expressed on 19%-27% of peripheral blood mononuclear cells (PBMC), 20%-30% of peripheral Thy 1+ T-lymphocytes, 40% of puppy thymocytes, 35%-45% of alloantigen-activated peripheral lymphocytes, and 100% of PBMC from a dog with acute T-cell leukemia. The antigen was not expressed on peripheral Thy 1- cells, bronchoalveolar cells, or null-type acute leukemia cells. The antibody inhibited cell-mediated lympholysis in the absence of complement, while antibody F3-20-7 directed at the canine Thy 1 antigen did not. It was not possible to precipitate a corresponding cell surface antigen on canine cells using standard 125I radioimmunoprecipitation techniques nor did the antibody cause antigenic modulation. Our data suggest that monoclonal antibody T811 reacts with a functional subset of canine T-lymphocytes similar to that of human cells; however, significant differences may exist between the antigens recognized on these cells in the two species.     

Activation and signaling status of human lamina propria T lymphocytes

In this study, proliferative responses of human lamina propria T lymphocytes were examined in vitro. The response of lamina propria T lymphocytes to Sepharose-bound anti-CD3 antibody plus interleukin 2 was significantly lower than the response of autologous peripheral blood T lymphocytes, whereas the responses of lamina propria T lymphocytes to anti-T11(2/3) antibodies plus sheep erythrocytes or anti-CD28 antibody plus interleukin 2 were largely preserved. After coculture with mucosa supernatant, peripheral blood T lymphocytes showed a similar pattern of reactivity as lamina propria T lymphocytes. This reduced reactivity to T-cell antigen receptor stimulation appears to exist at the level of signal transduction, because triggering of CD3 induces low amounts of intracellular inositol 1,4,5-triphosphate and no free calcium increase in lamina propria T lymphocytes when compared with peripheral blood T lymphocytes. This study indicates that the antigen receptor-dependent activation pathway of lamina propria T lymphocytes for proliferation is down-regulated by intestinal mucosa derived factor(s) and that the alternative pathways mediated by CD2 or CD28 are largely preserved. Based on previous data that lamina propria T lymphocytes can provide help to B cells, it is possible that these alternative activation pathways play an important role in T-B cell interaction in the gut.     

Myeloid-associated differentiation antigens on stem cells and their progeny identified by monoclonal antibodies

Within the hematopoietic system, monoclonal antibodies reactive with antigenic determinants, expressed in a lineage- and stage-restricted fashion, can be used to map myeloid differentiation. We have generated a series of monoclonal antibodies that reacts with myeloid-associated determinants on committed myeloid stem cells and their progeny. Their reactivity with peripheral blood cells was identified by immunofluorescence assays, with bone marrow cells by fluorescence- activated cell sorting, and with committed hematopoietic progenitor cells by both cytotoxic assays and fluorescence-activated cell sorting. Antibody 1G10, which has previously been reported to react with cells of the granulocytic lineage and with a minor subset of mature monocytes, was shown to react with granulocyte-macrophage colony- forming units (CFU-GM). Three antibodies not previously characterized (T5A7, L4F3, L1B2) were shown to react with both granulocytic and monocytic cells and in fluorescence-activated cell sorting studies to detectably stain granulocytic cells at different stages of maturation. These three antibodies also react with CFU-GM, two (L4F3 and L1B2) reacting with all CFU-GM, while T5A7 reacts with only a portion of the day 7 CFU-GM. Antibody L4F3 also reacts with a portion of erythroid burst-forming units (BFU-E). In contrast, the previously reported antibody 5F1, which reacts with monocytic cells, nucleated erythroid cells, and platelets, was shown to react with erythroid colony-forming units (CFU-E). Potential applications of these antibodies to studies of normal and malignant hematopoiesis are discussed.     

Myeloid differentiation antigen defined by a monoclonal antibody IF10

A monoclonal antibody of IgM class that defines the antigen present on human peripheral blood granulocytes was produced and characterized. This monoclonal antibody (IF10) was made from a single fusion between P3-X63-Ag8-U1 (P3U1) myeloma cells and splenocytes from a BALB/c mouse immunized against human cultured monocytoid cell line THP-1 cells. IF10-defined antigen(s) was expressed on the cells of granulocyte lineage such as peripheral blood granulocytes and metamyelocytes, myelocytes, promyelocytes, and a part of myeloblasts in the normal bone marrow, whereas it was not detected on resting and activated T lymphocytes, B lymphocytes, adherent monocytes, and thymocytes. The IF10-defined antigen was also expressed on cultured monocytoid cell lines as well as myeloid and myeloid/erythroid (K-562) cell lines. T lymphoblastoid cell lines, particularly those representing the T cells at an early thymocyte level, and a part of null cell lines were also reactive to IF10. Therefore, IF10 may be a unique monoclonal antibody that defines an antigen(s) which is expressed on almost whole stages of granulocytes and early stages of macrophages and T-cell lineages, and possibly during very early stages of erythroid lineage.     

Dickkopf-3, an immune modulator in peripheral CD8 T-cell tolerance

In healthy individuals, T cells react against incoming pathogens, but remain tolerant to self-antigens, thereby preventing autoimmune reactions. CD4 regulatory T cells are major contributors in induction and maintenance of peripheral tolerance, but a regulatory role has been also reported for several subsets of CD8 T cells. To determine the molecular basis of peripheral CD8 T-cell tolerance, we exploited a double transgenic mouse model in which CD8 T cells are neonatally tolerized following interaction with a parenchymal self-antigen. These tolerant CD8 T cells have regulatory capacity and can suppress T cells in an antigen-specific manner during adulthood. Dickkopf-3 (DKK3) was found to be expressed in the tolerant CD8 T cells and to be essential for the observed CD8 T-cell tolerance. In vitro, genetic deletion of DKK3 or blocking with antibodies restored CD8 T-cell proliferation and IL-2 production in response to the tolerizing self-antigen. Moreover, exogenous DKK3 reduced CD8 T-cell reactivity. In vivo, abrogation of DKK3 function reversed tolerance, leading to eradication of tumors expressing the target antigen and to rejection of autologous skin grafts. Thus, our findings define DKK3 as a immune modulator with a crucial role for CD8 T-cell tolerance.     

Reactivity of the monoclonal antibody RFB1 in chronic B-cell leukaemias

The monoclonal antibody RFB1, which reacts with early haemopoietic precursors in human bone marrow and peripheral T-lymphocytes, but not with pre-B cells and mature peripheral blood and marrow B lymphocytes, was tested in blood from 60 patients with chronic B cell leukaemias. All 37 cases of B chronic lymphocytic leukaemia (B-CLL) and 9 of hairy cell leukaemia (HCL) were positive. The antibody showed particularly strong reaction in HCL. On the other hand, RFB1 did not react with peripheral blood and B lymphocytes from 9 patients with non-Hodgkin lymphoma (NHL) in leukaemic phase and was negative or weakly expressed in 5 with prolymphocytic leukaemia (B-PLL). These findings may be significant for investigations on the cell origin of B-CLL and HCL. The reactivity of RFB1 was different from that of two anti-T1 monoclonal antibodies. The combined use of these reagents gave distinct patterns in B-CLL (RFB1+, T1+), HCL (RFB1++, T1-) and NHL and B-PLL (RFB1-/±, T1-/+), suggesting they may be of value in the differential diagnosis of these B-lymphoproliferative disorders.     

Inherited polymorphism of the human T-cell antigen receptor detected by a monoclonal antibody.

Three different murine monoclonal antibodies to the human clonotypic T-cell antigen receptor immunoprecipitate the alpha-beta chain heterodimer; induce comodulation of the clonotypic molecule with the T3 molecular complex; stain small populations of normal polyclonal T cells, suggesting that they react with variable or joining region determinants of the clonotypic receptor; and induce proliferation of resting T cells. While two of these antibodies detect the clonotypic receptor in all individuals studied, the third antibody (OT145), described herein, does not detect the T-cell antigen receptor on T cells of all individuals. By indirect immunofluorescence, three groups can be distinguished within a population of individuals (n = 138) by OT145. Individuals lacking T cells reactive with OT145 have a homozygous OT145-phenotype. T cells from such individuals fail to proliferate in the presence of OT145 in contrast to T cells from OT145+ individuals. Individuals with a relatively large percentage of OT145+ T cells, 4.5 +/- 1.54% (mean +/- 2 SEM) are homozygous OT145+, while those with an intermediate percentage, 2.04 +/- 0.9%, have a heterozygous phenotype. Family studies suggest autosomal codominant inheritance of the OT145 phenotype. The distribution of the three OT145-defined phenotypes varies considerably in populations of different ethnic background. Taken together these data suggest that the polymorphism detected by OT145 may represent a variable or joining region allotypic system of the human T-cell antigen receptor. In addition, our results indicate that allelic exclusion governs the expression of the clonotypic receptor by human T cells.     

Immunologic characterization of a helper T-cell lymphoma

The lymphocytes of a patient with a T-cell non-Hodgkin's lymphoma with peripheral blood involvement and polyclonal hypergammaglobulinemia were characterized in terms of surface markers and immunologic functions. Using the fluorescence-activated cell sorter and employing various monoclonal antibodies against T-cell surface antigens, it was shown that almost all of the patient's peripheral blood lymphocytes were positive for OKT4 and 9.3, antibodies that recognize helper T-cell subset. The circulating lymphoma cells had typical characteristics for T cells; they formed spontaneous rosettes with sheep erythrocytes and stained with the pan-T-cell antibodies 9.6 and 10.2, but did not react with other anti-T-cell monoclonal reagents such as OKT3, UCHT-1, and 3A1. The cells appeared to be mature by the fact that they did not stain with OKT6, and terminal deoxynucleotidyl transferase was undetectable. Functionally, they were able to provide "help" for antibody production, and they could be stimulated to produce moderate amounts of interleukin-2, while unable to proliferate in response to mitogens. Morphologically, some of the lymphocytes showed a deeply cleaved nucleus.     

Molecular heterogeneity of gamma delta T-cell antigen receptors expressed by CD4- CD8- T-cell clones from normal donors: both disulfide- and non-disulfide-linked receptors are delta TCS1+.

We investigated the molecular heterogeneity of gamma delta T-cell antigen receptors (TCR) expressed on T-cell clones generated from peripheral blood lymphocytes of normal donors. Extensive molecular heterogeneity was seen at the gamma-chain level and, to a lesser extent, at the delta-chain level. Both disulfide and non-disulfide gamma delta TCR were found and use different gamma chains with similar molecular masses (range, 41-43 kDa). In contrast, gamma chains of 55-60 kDa, which are expressed on T-cell lines derived from the peripheral blood of patients with immunodeficiency disorders, were not found on T-cell clones derived from the peripheral blood of normal donors. delta chains expressed on these T-cell clones had a molecular mass of 37 kDa and were either disulfide or nondisulfide linked. Significant delta-chain heterogeneity was identified in these clones using the anti-delta TCS1 and the anti-TCR delta 1 monoclonal antibodies. All clones tested were TCR delta 1+, whereas only 25% of the clones were delta TCS1+. The anti-delta TCS1 monoclonal antibody stained and immunoprecipitated both disulfide- and non-disulfide-linked gamma delta TCRs from different T-cell clones from normal donors.     

Increased density of ecto 5' nucleotidase antigen on leukemic T cells from patients with cutaneous T-cell lymphoma and adult T-cell leukemia/lymphoma

Malignant CD4+ T cells in adult T-cell leukemia/lymphoma (ATL) and cutaneous T-cell lymphoma (CTCL) express a number of cell surface molecules that are upregulated on normal T cells activated by foreign antigen. In this report we describe an interesting exception to the parallel phenotypic features of activated T cells and malignant CD4+ T cells. A monoclonal antibody (MoAb; termed 27.2) that was raised to HTLV-1+, CD4+25+ leukemic T cells stained weakly 25% of peripheral T cells, including approximately 50% of CD8+ T cells and 20% of CD4+ T cells. Flow cytometry analysis indicated that the surface density of the 27.2 antigen was unchanged or diminished when normal T cells were activated by antigen. However, 3/4 Sezary cases and 4/8 cases of ATL had relatively high densities of the 27.2 antigen. Immunoprecipitation and sodium dodecylsulfate polyacrylamide gel electrophoresis of the NP-40-solubilized membranes of surface-iodinated ATL cells indicated that MoAb 27.2 reacted with a 75 Kd molecule. The size and distribution of the 27.2 antigen on T cell subsets suggested that it might be the enzyme ecto-5' nucleotidase (NT), a phosphatidylinositol-linked enzyme that catalyzes dephosphorylation of monophosphate nucleotides to their respective nucleosides. This was confirmed by demonstrating that lymphocyte ecto-5'NT activity was blocked partially and inhibited completely by preincubating cells with MoAb 27.2 for 1 hour at 4 degrees C and 24 hours at 37 degrees C, respectively. When used with a second MoAb (27.1) to a novel T cell activation antigen found on all CTCL and ATL leukemias examined, 27.2 was found to discriminate between normal and leukemic T cells in two patients with ATL. These studies suggest that ecto-5'NT has diagnostic value in T cell malignancies and may be aberrantly expressed in some cases of ATL and CTCL.     

Monoclonal antibody that defines a unique human T-cell leukemia antigen

We have generated and characterized a hybridoma monoclonal antibody, termed SN1, that defines a unique human T-cell leukemia antigen. This antibody was generated by using a human leukemia antigen preparation isolated from cell membranes of MOLT-4, a leukemia T-cell line derived from a patient with T-cell-type acute lymphoblastic leukemia (T-ALL). SN1 was characterized by a sensitive microscale radioimmunoassay using a variety of cultured and uncultured human cells. In selected cases, the cell specimens were further tested by immunoperoxidase staining and an immunofluorescence staining test. The results of the radioimmunoassay were in agreement with those of the two other tests. Among the various cultured malignant and nonmalignant cell lines, SN1 reacted only with leukemia T-cell lines derived from patients with T-ALL; it reacted with all six T-ALL cell lines tested-i.e., JM, CCRF-CEM, CCRF-H-SB2, RPMI 8402, PEER, and MOLT-4. In the case of uncultured cell specimens derived from cancer patients, SN1 reacted with four of four cases of T-ALL but did not react with specimens derived from 41 patients with other types of cancer. SN1 did not react with any normal human cell specimens tested, both cultured and uncultured. These specimens include normal lymphoblastoid cell lines, thymocytes, bone marrow cells, spleen cells, lymph node cells, peripheral blood mononuclear cells, lymphocytes containing B and T cells, purified T cells, monocytes, granulocytes, erythrocytes, and platelets. Furthermore, SN1 did not react with phytohemagglutinin-activated T cells nor with concanavalin A-activated T cells. The results show that monoclonal antibody SN1 defines a type of human leukemia antigen that is expressed on the cell surface of T-cell-type ALL cells. The results further show the usefulness of SN1 in the diagnosis of cancer patients and suggest its therapeutic potential. We designate this antigen TALLA, a T-cell ALL antigen.     

Human monoclonal antibody directed against an envelope glycoprotein of human T-cell leukemia virus type I.

We report the production and characterization of a human monoclonal antibody reactive against the major envelope glycoprotein of human T-cell leukemia virus type I (HTLV-I), a virus linked to the etiology of adult T-cell leukemia. We exposed lymph-node cells derived from a patient with adult T-cell leukemia to the Epstein-Barr virus in vitro and obtained a B-cell clone (designated 0.5 alpha) by a limiting dilution technique. The secreted product of 0.5 alpha is a monoclonal antibody (also designated 0.5 alpha; that is IgG1 and has kappa light chains) that binds to the cell membrane of T-cells infected with HTLV-I and lyses them in the presence of complement. The antibody does not react with HTLV-I-negative T cells. In electroblot assays, the monoclonal antibody detects a 46-kDa glycoprotein in disrupted HTLV-I virions and a 34-kDa product following digestion of the viral protein with endoglycosidase F. These molecules have been reported to represent the HTLV-I env gene products. The antibody does not react with HTLV-II and HTLV-III virions. Glycoproteins of 61 and 68 kDa, which are known to be encoded at least in part by the env gene of HTLV-I, are precipitated by the antibody from endogenously radiolabeled HTLV-I-infected HUT 102-B2 and MT-2 cells, respectively. These results suggest that this human monoclonal antibody reacts with an env-encoded glycoprotein of HTLV-I. By using a competition assay with a biotin-labeled 0.5 alpha antibody, we observed that 15 out of 15 patients with adult T-cell leukemia had antibodies that block binding of the 0.5 alpha antibody to HTLV-I virions. This suggests that the antigen detected by 0.5 alpha antibody is a common epitope recognized in HTLV-I-infected individuals in vivo. This antibody, as well as the general strategy for making human monoclonal antibodies reactive against pathogenic retroviruses, may have diagnostic or therapeutic application.     

Differential expression of CD24-related epitopes in mycosis fungoides/Sézary syndrome: a potential marker for circulating Sézary cells.

In the hematopoietic system, the B-cell associated antigen CD24 is expressed at high density on B cells, B-cell precursors, and B-cell malignancies as well as at low density on peripheral blood polymorphonuclear leukocytes. The 42-Kd sialoglycoprotein has not been previously demonstrated to be expressed on T cells, thymocytes, or T-cell malignancies. We identified three patients with mycosis fungoides/Sézary syndrome that showed low density expression of the CD24-related epitope recognized by antibody BA-1 on circulating T cells. All three patients had Sézary cells by morphologic assessment and clonal T-cell populations in the peripheral blood by gene rearrangement studies. In two of these patients, indirect immunofluorescence with a panel of six anti-CD24 monoclonal antibodies demonstrated reactivity for two of six antibodies in one case and only one of six antibodies in the other. The biologic significance of CD24-related epitope expression on circulating T cells in mycosis fungoides/Sézary syndrome is unclear. However, these findings suggest that differential, low density expression of CD24-related epitopes (BA-1+, OKB2-) may be a useful phenotypic marker for identifying circulating Sézary cells.