Antibody OKT3 Research Articles

Acute Hypertension after Renal Allograft Rejection Therapy with OKT3 Monoclonal Antibody

Acute rejection of renal allografts was treated with the monoclonal antibody OKT3 given intravenously. A variety of adverse events were observed on days 1 and 2 following treatment with 5 mg/day OKT3 for 10 days including heart failure, pulmonary oedema and hypertension. Continuous monitoring of 19 patients treated with OKT3 for acute renal allograft rejection detected a transient increase, lasting 2 h, in systolic and diastolic blood pressures on day 1. A larger increase in systolic and diastolic pressures lasting 11-13 h was observed on day 2. Treatment with 5 mg OKT3 on day 3 did not significantly increase systolic or diastolic pressure. It is concluded that OKT3 can aggravate hypertension and hypertensive emergencies may be encountered during the initial phase of OKT3 treatment.

In vitro OKT3-induced mitogenesis in selenium-deficient patients on a diet for phenylketonuria

Patients with phenylketonuria (PKU) are frequently deficient in the essential trace element selenium (Se), because of their very low protein diet. Using two approaches to investigate T-cell response to proliferative signaling, viz, mitogenesis caused by the monoclonal antibody OKT3 and the plant lectin phytohaemagglutinin (PHA), we demonstrated significantly reduced responses to optimal concentrations of OKT3 in a group of PKU patients with reduced serum Se compared with a normal group (p = 0.0005) and with a group of PKU patients whose serum Se was normal (p = 0.0023). The response of the Se-deficient group to optimal levels of PHA did not differ from that of the normal controls or from that of Se-normal PKU patients. A dose-dependent relationship between serum Se levels and mitogenic response was evident for OKT3 (r = 0.34, p = 0.0154), but not for PHA (r = -0.02, p = 0.9086). We suggest that the reduced response to OKT3 mitogenesis in Se-deficient PKU patients is possibly the consequence of impaired Se-dependent metabolic activity, which affects mitogenic signaling via the T cell antigen receptor (TCR/CD3) complex.

Human T-lymphoblastoid cells selected for growth in serum-free medium provide new tools for study of HIV replication and cytopathogenicity

Human T-lymphoblastoid cells H9, CEM and CEM-clone 5 were selected for growth in RPMI 1640 supplemented with transferrin 5 μg/ml, insulin 5 μg/ml and sodium selenite 5 ng/ml. After 40 days of adaptation to serum-free medium, these cells displayed growth, morphology, and expression of CD4 similar to serum-supplemented cultures. Infection of these cells with two strains of HIV-1 (LAV and NDK) and a strain of HIV-2 (ROD) was as efficient in serum-free as in serum-supplemented medium as demonstrated by reverse transcriptase activity in the culture supernatants of infected cells. Furthermore, HIV-induced cytopathogenicity was observed in serum-free cultures, demonstrating that both HIV infection and cytopathic effect did not require the presence of serum components. Electron microscopy showed that mature viral particles were produced from infected cells cultured in serum-free medium. Finally, the ability of monoclonal antibody OKT4 A to inhibit infection by HIV-1 LAV but not by HIV-1 NDK was the same with and without serum in the culture medium, demonstrating that both CD4-dependent and CD4-independent infections can occur in the total absence of serum. Human T-lymphoblastoid cells adapted for growth in serum-free medium provide therefore a complementary tool for the study of HIV infection and cytopathogenicity under defined conditions.

In Situ Hybridization of Interferon‐Gamma Producing Peripheral Blood Mononuclear Cells

Individual interferon-gamma (IFN-gamma) producing cells in activated human peripheral blood mononuclear cells (PBMC) were characterized by in situ hybridization using [35S]-labelled antisense RNA probes. The proportion of positive cells expressing IFN-gamma mRNA varied according to the substances used for stimulation. IFN-gamma mRNA expressed a relatively low percentage of 1-8% PBMC after a single stimulus with mitogens or OKT-3 antibody and 20-30% of the cells were identified to synthesize IFN-gamma mRNA after stimulation with PHA + P-MA + OKT-3 antibody. The expression of IFN-gamma mRNA and production of the lymphokine was dependent on accessory cells. If accessory cells were replaced by recombinant interleukin-1 (IL-1) plus interleukin-6 (IL-6), then T-cell proliferation to phytohaemagglutinin (PHA) could be partially restored and measurable amounts of IFN-gamma were detected. The addition of interleukin-2 (IL-2) or phorbol-12-myristate-13-acetate to T cells stimulated with PHA, IL-1 and IL-6 did not restore the production of IFN-gamma to an extent comparable to that produced by T cells stimulated in the presence of accessory cells. In further studies, depletion of T-cell subsets showed that CD3+, CD4+, CD8+, CD29+ and CD45RA+ cells were involved in IFN-gamma production after mitogenic stimulation. In conclusion, our data demonstrate that IFN-gamma production is dependent on signals from accessory cells and IFN-gamma is synthesized by only a small proportion of T cells, that did not belong to a unique population, characterized by conventional cellular surface antigens.

Monoclonal and polyclonal antibodies: clinical aspects

Over the years, the ways in which the antibodies ATG and OKT3 have been used in clinical transplantation have changed. ATG was first on the scene and has been used as initial immune suppression in certain forms of transplantation, of which cardiac transplantation is one good example. It has not been commonly used in renal transplantation, but there is evidence that this may be changing. The nephrotoxic side-effects of cyclosporin continue to cause anxiety, and high rates of initial non-function of kidney allografts have made early management difficult; this may have contributed to some early graft failures. There is currently interest in avoiding the use of cyclosporin initially by commencing immune suppression treatment with ATG, in an attempt to improve the immediate function rate of kidney grafts. When function is established, more conventional treatment schedules, usually with cyclosporin A, are introduced. ATG is also being incorporated in basic immunesuppressive regimes as part of multiple drug treatments. The hypothesis of multiple drug treatments is based on the idea that if a number of different immune suppressive agents are used, then the dose of each may be reduced, with minimisation of side-effects. This concept may be true, but the price may be that of an increased rate of malignancy in the long-term graft recipients.(ABSTRACT TRUNCATED AT 250 WORDS)

Remote T cell co‐stimulation via LFA‐1/ICAM‐1 and CD2/LFA‐3: Demonstration with immobilized ligand/mAb and implication in monocyte‐mediated co‐stimulation

Proliferative response of resting T cells generally requires not only cross-linking of the T cell receptor (TcR) but also co-stimulatory signals from accessory molecules. We here have used a "three-cell" model consisting of: (a) resting human CD4+ T cells as responders; (b) CD3 monoclonal antibody (mAb) OKT3 on latex beads as surrogate stimulators; (c) autologous monocytes as source of co-stimulation. As described by Kawakami et al. (J. Immunol. 1989, 142: 1818), T cell proliferation in this system is observed with paraformaldehyde-fixed monocytes if they have been activated and interleukin (IL) 1 beta/IL 6 is supplied. Since this three-cell system provides TcR cross-linking at a site spatially "remote" from co-stimulation, they help distinguish adhesion from signal transduction but the molecules that mediate co-stimulation in this system have not been identified. Our studies now demonstrate that co-stimulation by the monocytes is dependent on each of two receptor/ligand pathways CD2/LFA-3 and LFA-1/ICAM-1 since it is inhibited by each relevant mAb but not a variety of control mAb. The hypotheses that CD2 and LFA-1 could each mediate co-stimulation was tested in simplified model systems in which the monocyte was replaced with immobilized CD2 mAb or purified ICAM-1 presented on a separate surface from the CD3 mAb. The results in these simplified models demonstrate that on resting T cells either CD2 or LFA-1 molecules alone can mediate "remote" co-stimulation unlike most other T cell surface molecules. Co-stimulation requires IL 1 beta/IL6 both in the weaker LFA-1 ligand-mediated co-stimulation and at lower CD2 mAb concentrations in the stronger CD2 mAb-mediated co-stimulation. Thus: (a) the accessory cell function of stimulated fixed monocytes in T cell proliferation requires both the LFA-1/ICAM-1 and CD2/LFA-3 pathways; and (b) the T cell molecules CD2 and LFA-1 can give co-stimulatory signals that can act in a "remote" fashion.

Plasma membrane and intracellular pools of transferrin receptors decline during in vitro cultivation of U937 cells

Transferrin receptor expression in the monocyte-like cell line U937 was investigated during in vitro cultivation. U937 cells expressed a single class of high affinity surface transferrin receptors (KD approximately 4 nM), with apparent subunit Mr of 90-95,000 Da as determined by SDS-reducing PAGE. [125I]-transferrin binding studies on detergent-solubilized cells revealed that half to two-thirds of the total functional binding sites were located intracellularly. Radioligand binding, immunofluorescence and flow cytometry studies were performed on intact, detergent-solubilized, or saponin-permeabilized cells, using either transferrin or the anti-transferrin receptor monoclonal antibody OKT9 IgG. These studies demonstrated that functional and antigenic transferrin receptor levels were maximal on cells 24 h after subculture at low density and declined during the culture period. Scatchard analysis of radioligand binding data suggested that the decline in functional transferrin binding sites resulted from a decline in the number of available receptors. These results demonstrate that in U937 cells there is a density-dependent regulation of transferrin receptor expression, resulting in a loss of functional and antigenic receptors from both plasma membrane and intracellular locations.

CD4-mediated stimulation of human eosinophils: lymphocyte chemoattractant factor and other CD4-binding ligands elicit eosinophil migration.

Lymphocyte chemoattractant factor (LCF) is a tetrameric glycoprotein of 56,000 relative molecular mass produced by activated T lymphocytes. LCF binds to CD4 and has previously been found to stimulate migration of CD4+ lymphocytes and monocytes. Because human eosinophils, like T cells and monocytes, express CD4, we examined functional responses of eosinophils to LCF. Recombinant LCF (rLCF) expressed in COS cells was purified on a CD4 affinity column. Migration of eosinophils was elicited by rLCF at low concentrations: the 50% effective dose (ED50) was 10(-12) to 10(-11) M, concentrations 100- to 1,000-fold lower than the ED50s for the recognized eosinophil chemoattractants C5a and platelet-activating factor. Two other ligands which bound to CD4, human immunodeficiency virus-1 envelope glycoprotein gp120 and monoclonal antibody OKT4, also stimulated eosinophil migration. Monovalent OKT4 Fab competitively inhibited eosinophil responses to rLCF. rLCF did not influence other functional responses of eosinophils tested, including degranulation, superoxide generation, leukotriene C4 production, in vitro survival, or surface expression of the adherence receptor CR3 (CD11b), human histocompatibility leukocyte antigen DR, or interleukin 2 receptor p55 (CD25). We conclude that CD4 on eosinophils is capable of transducing a migratory stimulus and serves as a receptor for a chemoattractant lymphokine LCF. T cell-derived LCF may contribute to recruitment of eosinophils and CD4+ mononuclear cells concomitantly at inflammatory reactions.

Lateral diffusion of CD4 on the surface of a human neoplastic T-cell line probed with a fluorescent derivative of the envelope glycoprotein (gp120) of human immunodeficiency virus type 1 (HIV-1)

The envelope glycoprotein (gp120) of HIV-1 was labeled with fluorescein by using 6-[4,6-dichlorotriazinyl]aminofluorescein. The labeled glycoprotein was found to bind to CD4-positive CEM cells. Monoclonal antibody OKT4a but not OKT4 blocked this binding. Similar specific binding of fluorescein-labeled gp120 with CD4 was observed in a solid-phase ELISA where sCD4 was attached to a polystyrene plate. The syncytium formation induced by HIV-1-infected cells on CEM cells was significantly inhibited in the presence of fluorescein-labeled gp120. Fluorescence photobleaching recovery measurements showed that the diffusion coefficient (D) of CD4 molecules complexed with fluorescein-labeled gp120 was approximately 5 x 10(-10) cm2sec-1, with nearly 61% of the receptor molecules being mobile. Binding of anti-gp120 monoclonal antibody to the CD4-gp120 complex reduced the mobile fraction significantly. Diffusion of CD4 labeled with OKT4 IgG was markedly inhibited with reductions in both D and the mobile fraction, but such inhibition was not observed with OKT4 Fab. It appears that crosslinking of multiple molecules of CD4 by OKT4 antibody is required to reduce CD4 mobility. This suggests that the receptor might be present on the membrane plane as molecular clusters containing at least two molecules of CD4.

Vitamin D receptor expression in human lymphocytes. Signal requirements and characterization by western blots and DNA sequencing.

The signals controlling the expression of the receptor protein for 1 alpha,25-dihydroxyvitamin D3 in normal human lymphocytes and the relationship of this protein to the classical vitamin D receptor were examined. Lymphocytes activated with the OKT3 antibody to the T-cell antigen receptor expressed fewer binding sites as compared to lymphocytes that were activated by the polyclonal activator phytohemagglutinin (PHA). However, combination of OKT3 and phorbol myristate acetate produced a concentration of binding sites similar to the PHA-activated cells. The receptor from OKT3 and OKT3 + phorbol myristate acetate-activated lymphocytes exhibited decreased binding to DNA-cellulose compared to PHA-activated lymphocytes. In lymphocytes activated either by PHA or OKT3 (but not in resting cells), a 50-kDa species cross-reacting with a monoclonal antibody against the intestinal vitamin D receptor was detected. Finally, RNA from activated lymphocytes was amplified by polymerase chain reaction using oligonucleotide primers flanking the 196 base pair long region encoding the DNA-binding domain of the human intestinal receptor. The amplified product showed an identical nucleotide sequence to the DNA-binding domain of the human intestinal receptor. These findings suggest that expression of the 1,25-(OH)2D3 receptor in lymphocytes is triggered by distinct and contingent signals, and that the protein and the mRNA encoding it are identical to the classical vitamin D receptor.

Preliminary studies for an immunotherapeutic approach to the treatment of human myeloma using chimeric anti-CD38 antibody

Multiple myeloma is a disease in which conventional chemotherapy has only limited value, but which may be ideal for treatment with passive antibody against a suitable cell surface antigen on the neoplastic plasma cell. The CD38 antigen is known to be present on the majority of neoplastic plasma cells, and this was confirmed by detailed examination of bone marrow aspirates from three patients. Strong expression of CD38 was confined to cells which, by the criteria of light-scattering profiles and possession of cytoplasmic Ig, were plasma cells. The vast majority of neoplastic plasma cells appeared to be involved. Using a cell line as a model, it was found that the CD38 antigen acts as a target for a chimeric antibody prepared from the antibody OKT10. The chimeric antibody consists of the Fab portion of the mouse monoclonal antibody linked by a stable thioether bond to an Fc molecule derived from human IgG1, thereby forming mouse Fab-human Fc. In contrast to the parent antibody, the chimeric molecule mediates antibody-dependent cellular cytotoxicity (ADCC) very efficiently with human blood mononuclear effector cells, and is effective at low concentration. Also, even though the CD38 antigen is present on natural killer cells, there appears to be little deleterious action of the antibody on effector cell function. The antibody also failed to affect the growth of progenitor cells of the granulocyte/macrophage or erythroid lineages present in normal bone marrows, despite the suspicion that these cells express the antigen. Other advantages of the CD38 molecule are that it is not found in the serum of patients with myeloma, and it does not appear to modulate in vitro. Fourteen patients with florid myeloma and on various chemotherapeutic regimes had an undiminished capacity to mediate ADCC with the chimeric antibody, when compared with normal individuals. The maintenance of ADCC activity, coupled with the known suppression of the antibody response in these patients, augers well for treatment with chimeric antibody.

Preliminary Studies for an Immunotherapeutic Approach to the Treatment of Human Myeloma Using Chimeric Anti-CD38 Antibody

Multiple myeloma is a disease in which conventional chemotherapy has only limited value, but which may be ideal for treatment with passive antibody against a suitable cell surface antigen on the neoplastic plasma cell. The CD38 antigen is known to be present on the majority of neoplastic plasma cells, and this was confirmed by detailed examination of bone marrow aspirates from three patients. Strong expression of CD38 was confined to cells which, by the criteria of light-scattering profiles and possession of cytoplasmic Ig, were plasma cells. The vast majority of neoplastic plasma cells appeared to be involved. Using a cell line as a model, it was found that the CD38 antigen acts as a target for a chimeric antibody prepared from the antibody OKT10. The chimeric antibody consists of the Fab portion of the mouse monoclonal antibody linked by a stable thioether bond to an Fc molecule derived from human IgG1, thereby forming mouse Fab-human Fc. In contrast to the parent antibody, the chimeric molecule mediates antibody-dependent cellular cytotoxicity (ADCC) very efficiently with human blood mononuclear effector cells, and is effective at low concentration. Also, even though the CD38 antigen is present on natural killer cells, there appears to be little deleterious action of the antibody on effector cell function. The antibody also failed to affect the growth of progenitor cells of the granulocyte/macrophage or erythroid lineages present in normal bone marrows, despite the suspicion that these cells express the antigen. Other advantages of the CD38 molecule are that it is not found in the serum of patients with myeloma, and it does not appear to modulate in vitro. Fourteen patients with florid myeloma and on various chemotherapeutic regimes had an undiminished capacity to mediate ADCC with the chimeric antibody, when compared with normal individuals. The maintenance of ADCC activity, coupled with the known suppression of the antibody response in these patients, augers well for treatment with chimeric antibody.

Lymphoreticular cells in invasive carcinoma of the uterine cervix: an immunohistological study

In the present study the immunohistology of the cellular stromal reaction of invasive squamous cell carcinoma of the cervix is investigated. Tumor tissue from 10 patients with invasive squamous cell carcinoma of the uterine cervix (stages Ib–IIb, according to FIGO) was immunostained by the alkaline phosphatase-anti-akaline phosphatase (APAAP) method. The monoclonal antibodies OKT3, OKT4, OKT8, TO15, Ki-M 1, and Ki-M 6 were applied. The cells in the stroma and the tumor foci were evaluated separately. In all cases, the overwhelming majority of lymphoreticular cells were found in the stroma and the tumor-cell complexes contained relatively low numbers of these cells. While B-lymphocytes were present only in low numbers or were virtually absent from the lymphoreticular infiltrates, cells of the mononuclear-phagocyte system were found to be another prominent constituent of the tumor's cellular stromal reaction.

Tumor-cell lysis byin-situ-activated human peripheral-blood mononuclear cells

A heteroconjugate (HC) was synthesized between OKT3 and monoclonal antibody (MAb) 7E8, which specifically reacts with the tumor marker placental alkaline phosphatase (PLAP). Similarly to OKT3, in vitro, the HC induced a dose-dependent proliferation response of human peripheral-blood mononuclear cells (PBMCs) and, in concert with rIL-2, it progressively activated T cells over a 4-day period. In co-cultures of continuously activated PBMCs and MO4 tumor cells (non-MHC-restricted mouse fibroblasts transfected with the cDNA for PLAP), the HC (25 ng/ml), again acting in concert with rIL-2, induced specific lysis of the MO4 cells. This process occurred progressively over 2 to 3 days and was monitored from the release in the supernatant fluid of cellular 3H-L-leucine, but also from analyses involving the remaining non-lysed cancer cells, i.e., by estimates of their protein content, by measurements of their viability, and most accurately by determinations of their PLAP content. Antibody 7E8 by itself induced a weak tumor-cell lysis (ADCC), potentiated by the addition of rIL-2. However, after 7 days of PBMC-preactivation with the HC and rIL-2, antibody 7E8 no longer mediated any ADCC, whereas the HC-dependent lysis was further potentiated. The observed proliferation of T cells and development of cytotoxicity at low concentrations of HC and rIL-2 support the idea that a moderate but continuous T-cell activation combined with T-cell targeting is sufficient for the induction of progressive and efficient tumor-cell lysis.

Muromonab CD-3: a review of its pharmacology, pharmacokinetics, and clinical use in transplantation.

Muromonab CD-3 (OKT-3) is a monoclonal antibody that is highly effective in the treatment of acute rejection in solid organ transplants. Due to its monoclonal nature, each molecule is identical because it is derived from a single antibody-producing clone. OKT-3 is administered only by intravenous injection and has a harmonic half-life of approximately 18 hours. It binds specifically to the CD-3 complex, which is involved in antigen recognition and cell stimulation, on the surface of T lymphocytes. Immediately after administration CD-3-positive T lymphocytes are abruptly removed from the circulation. The route of metabolism for OKT-3 is not clear; it may be removed by opsonization by the reticuloendothelial system when bound to T lymphocytes, or by human antimurine antibody production. The agent has been effective in reversing corticosteroid-resistant acute rejection in renal, liver, and cardiac transplant recipients. Its use in pancreatic and bone marrow recipients is inconclusive. OKT-3 has a considerable number of initial side effects, and some life-threatening reactions may occur. This drug should not be administered to any patient who is greater than 3% usual body weight because of the potential for the development of severe pulmonary edema. OKT-3 may also be associated with a high rate of infection, especially of the viral type. The usual dose is 5 mg administered as an intravenous bolus over 2-4 minutes daily for 10-14 days. Approximately 85% of patients treated with OKT-3 develop reactive human antimurine antibodies that, over time, may lead to tachyphylaxis and neutralization of the murine antibody OKT-3. OKT-3 is potent immunosuppressive agent and is an important prototype of future monoclonal antibodies.

OKT3 first-dose reaction: Association with T cell subsets and cytokine release

Use of the monoclonal antibody OKT3 to prevent or treat allograft rejection has become commonplace. Its administration is often complicated by serious side effects, usually occurring within one to two hours after OKT3 is given, and is termed first-dose reaction. The mechanism underlying these signs and symptoms is poorly defined, but may be related to cytokine release. Twenty-three kidney or kidney/pancreas transplant recipients received OKT3 as treatment of acute rejection. Signs and symptoms occurring after the first dose were observed and quantitated prospectively, and a reaction score was calculated. Blood was drawn immediately before, and at 2 and 24 hours after the first dose of OKT3 for determination of interleukin-2 (IL2), interferon-gamma (IFN gamma), and tumor necrosis factor-alpha (TNF alpha) levels, and flow cytometric analysis of T cell subsets. Two groups were defined based on severity of first-dose reaction. Group 1 patients (N = 11) had very mild reactions (reaction score less than or equal to 3); Group 2 patients (N = 12) had more severe reactions (score greater than or equal to 5). All patients demonstrated a significant rise in serum TNF alpha from baseline to two hours after OKT3 (9 +/- 3 pg/ml to 378 +/- 54 pg/ml, P less than 0.0001), and there was significant correlation between reaction scores and two-hour TNF alpha levels (P = 0.005). Group 2 patients had higher TNF alpha levels at two hours than did Group 1 patients (484 +/- 75 pg/ml vs. 263 +/- 62 pg/ml, P = 0.04). Levels of IL2 and IFN gamma were not elevated at any sampling time.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Rejection Therapy in Renal Transplantation: Use of the Monoclonal Antibody OKT3

The success of anti-rejection therapy was evaluated in 65 cadaveric renal allografts immunosuppressed with cyclosporin. All first rejection episodes were treated with 0.5 g methylprednisolone given daily for 3 days. Second rejection episodes were treated with either a further identical 3-day course of methylprednisolone or a 10-14-day course of the monoclonal antibody OKT3. The peak creatinine during second rejection episodes was higher in patients treated with OKT3 (481 +/- 54 mumol/l; mean +/-SEM) than in those treated with methylprednisolone (320 +/- 59 mumol/l) (P = 0.036), suggesting more severe rejection in the OKT3 group. Despite this the rejection reversal rate was higher in the OKT3-treated group (100%) when compared to the high-dose methylprednisolone group (64%) (P less than 0.05) and the creatinine at 6 months was less in the OKT3 group (162 +/- 17 mumol/l) than in the methylprednisolone group (230 +/- 22 mumol/l). These data suggest that OKT3 is a very effective treatment for second rejection episodes following renal transplantation and yields improved renal functions in comparison with high-dose steroids.

Reversal of acute glomerular renal allograft rejection: a possible effect of OKT3

A major cause of renal allograft loss is glomerulovascular rejection. This case report is about an episode of histologically proven acute glomerular rejection that was successfully reversed. Monoclonal antibody OKT3 may have been the effective agent.

Reversal of acute glomerular renal allograft rejection: a possible effect of OKT3

Abstract. A major cause of renal allograft loss is glomerulovascular rejection. This case report is about an episode of histologically proven acute glomerular rejection that was successfully reversed. Monoclonal antibody OKT3 may have been the effective agent.

リンパ節およびひ臓内Ｔ領域における樹状細胞の免疫組織化学的研究

Langerhans cells (LCs) in the epidermis and interdigitating reticulum cells (IDCs) in the lymph nodes are said to have the same morphological and immunological characteristics. In this paper, we examined LCs and IDCs in the superficial (cervical and inguinal), hilar and mesenteric lymph nodes, and also spleens, using anti S-100 protein and OKT-6 antibodies for immunostaining. Lymph nodes and spleens taken from 16 autopsies were used for the experiments. We were able to observe LCs which were positive for both anti S-100 protein and OKT-6 in the superficial and hilar lymph nodes. However, we could not find LCs in the mesenteric lymph nodes or spleens. The immunological and morphological features of LCs were similar to those of veiled cells in the marginal sinus possibly moving from the skin to the T-zone of the superficial and hilar lymph nodes. OKT-6 positive cells were not exactly identical with anti S-100 protein positive cells, because the total number of S-100 protein positive cells was greater than that of OKT-6 positive cells. The existence of a larger number of OKT-6 positive cells in the inguinal lymph nodes than in the cervical lymph nodes may be because there are more opportunities for the lower extremities to receive different kinds of stimuli than for the head. LCs may receive some stimulation from the external environment and/or retain antigens. LCs might also be responsible for T cell dependent immune responses. Our results suggest that LCs and IDCs have slightly different immunological characteristics, and therefore, they may have some different functions.