Biomedical subjects

C Morimoto

Publications and source records attributed to C Morimoto.

At least 127 records · Page 7Linked to original sources

PubMed1994

Prolonged impairment of very late activating antigen-mediated T cell proliferation via the CD3 pathway after T cell-depleted allogeneic bone marrow transplantation.

One of the major obstacles in allogeneic bone marrow transplantation (allo-BMT) is prolonged T cell dysfunction resulting in a variety of infectious complications in the months to years after hematologic engraftment. We previously showed that immobilized extracellular matrix (ECM) proteins such as fibronectin (FN), the CS-1 domain of FN, or collagen (CO) acted synergistically with immobilized anti-CD3 to induce T cell proliferation. In addition, the comitogenic effect of ECMs could be mimicked by immobilized mAb reactive with a common beta 1 chain (CD29) of very late activating (VLA) antigens which include ECM receptors. Since the interaction of T cells with ECMs appears to play an important role in the process of T cell reconstitution following allo-BMT, we examined the expression of VLA antigens (alpha 1-alpha 6, beta 1) and their functional roles in CD3-mediated T cell proliferation at various times after T cell depleted allo-BMT. VLA beta 1 as well as VLA alpha 4, alpha 5, and alpha 6 expression was lower than normal controls during the first 3 mo after allo-BMT and auto-BMT, whereas these expressions returned to normal levels by 4 mo after allo-BMT and auto-BMT. Although alpha 1 and alpha 2 were not expressed on lymphocytes from normal controls, these antigens were expressed on lymphocytes at the detectable levels (5-15%) from patients after allo-BMT and auto-BMT. Both CD29 and CD3 were expressed at normal levels on lymphocytes from patients > 3 mo after allo-BMT, whereas T cell interaction with ECM through VLA proteins or crosslinking of VLA beta 1 expressed by T cells with anti-CD29 mAb results in poor induction of CD3-mediated T cell proliferation for a prolonged period (> 1 yr) after allo-BMT. In contrast, T cell proliferation induced by crosslinking of anti-CD2 or anti-CD26 with anti-CD3 was almost fully recovered by 1 yr post-allo-BMT. After autologous BMT, impaired VLA-mediated T cell proliferation via the CD3 pathway after auto-BMT returned to normal levels within 1 yr despite no significant difference in CD3 and CD29 expression following either allo- or auto-BMT. The adhesion of T cells from post-allo-BMT patients to FN-coated plate was normal or increased compared to that of normal controls. Moreover, the induction of the tyrosine phosphorylation of pp105 protein by the ligation of VLA molecules was not impaired in allo-BMT patients. These results suggest that there are some other defects in the process of VLA-mediated signal transduction in such patients. Our results imply that disturbance of VLA function could explain, at least in part, the persistent immunoincompetent state after allo-BMT and may be involved in susceptibility to opportunistic infections after allo-BMT.

Antigens, CD↗

PubMed1994

Adhesion of follicular lymphoma cells to lymphoid germinal centers--a potential mechanism of tumor cell homing following autologous transplantation.

Follicular non-Hodgkin's lymphomas (NHL) generally present as disseminated diseases with infiltration of lymphoid organs, bone marrow (BM), as well as peripheral blood (PB). These lymphoma cells may recapitulate the behavior of normal germinal center (GC) B cells, some of which remain in follicles and others which have the capacity to migrate. Normal activated B cells and follicular lymphoma cells bind to GCs in vitro and this interaction is mediated by VLA-4 on the lymphoid cell and VCAM-1 on follicular dendritic cells. Since the disseminated nature of follicular NHLs may be related to the ability of PB and BM cells to recirculate through lymphoid tissues, we examined the adhesive characteristics of follicular lymphoma cells isolated from these site. Cells from 10 of 14 cases of follicular NHL involving PB or BM bound to normal GCs. Neoplastic GCs could similarly support the binding of PB or BM derived follicular NHL cells. This interaction was inhibited by monoclonal antibodies directed against VLA-4 and VCAM-1. These studies may provide insight into the clinical behavior of these diseases. More importantly the homing and adhesion of lymphoma cells is likely to be relevant to the use of PB and BM as a source of hematopoietic stem cells following high dose ablative therapy.

Antibodies, Monoclonal↗

PubMed1994

Effect of substrates on the cyclic AMP-dependent lipolytic reaction of hormone-sensitive lipase.

Cyclic AMP-dependent activation of hormone-sensitive lipase (HSL) stimulated lipolysis of [3H]triolein emulsified with gum arabic, but not that of endogenous lipid droplets from rat fat cells. The absence of responsiveness of the lipid droplets to activation of HSL was found to be caused by some factor other than their surface area. The activated HSL showed a higher rate of lipolysis than nonactivated HSL on lipid droplets sonicated with gum arabic. Addition of phosphatidylcholine, which is one of the minor components of intact lipid droplets, to triolein or the sonicated lipid droplet emulsion induced loss of responsiveness to activated HSL, and treatment of these substrates containing phosphatidylcholine with phospholipase C restored the responsiveness. These results suggest that loss of responsiveness of the endogenous lipid droplets in fat cells to activated HSL may be due to phosphatidylcholine in the lipid droplets.

Adipose Tissue↗

PubMed1994

Role of endogenous lipid droplets in lipolysis in rat adipocytes.

Sonication of rat fat cells caused an increase in lipolysis in the absence of lipolytic stimulants (basal lipolysis) and loss of epinephrine responsiveness. Sonication of endogenous lipid droplets from fat cells also induced an increase in lipolysis in the presence of hormone-sensitive lipase (HSL) and loss of epinephrine responsiveness in a cell-free system consisting of lipid droplets and HSL. This increase in lipolysis was found not to be due to an increase in the surface area resulting from sonication, but seemed to be due to a decrease in the phosphatidylcholine concentration on the surface of the lipid droplets. Addition of phosphatidylcholine to the sonicated lipid droplets reduced the hydrolysis of triglyceride by HSL in the cell-free system, consisting of HSL and intact lipid droplets or a lipid emulsion containing phosphatidylcholine increased lipolysis. These results suggest that phosphatidylcholine on the surface of the lipid droplets may be a regulatory factor for lipolysis in fat cells.

Adipose Tissue↗

PubMed1993

Targeting of an activated T-cell subset using a bispecific antibody-toxin conjugate directed against CD4 and CD26.

We have developed a bispecific antibody that recognizes the CD4 and CD26 antigens simultaneously and that was examined for its ability to target CD4+CD26+T cells. These latter cells constitute the activated component of the CD4+ CD29highCD45RO+ memory T-cell subset that provides help for B-cell Ig synthesis and help for responses against recall antigens. The purified bispecific antibody exhibited an estimated dissociation constant (kd) of 2.4 x 10(-9) mol/L, on comparison with 1.1 x 10(-9) mol/L for anti-CD26, and 1.6 x 10(-10) mol/L for anti-CD4. Surface plasmon resonance was used to show the bifunctional capacity of the antibody. On binding 125I-bispecific antibody to phytohemagglutinin (PHA)-activated T cells, 54.4% of the bound antibody was internalized. This was the result of bispecific binding, because monovalent fragments of anti-CD4 and anti-CD26 were not able to modulate antigen or induce internalization using both a fluorescent assay and an 125I-internalization assay. The ability of the bispecific antibody to be internalized was used to deliver a toxin, blocked ricin, specifically to cells that are CD4+CD26+. The inability of monovalent fragments to be internalized formed the basis for our hypothesis that monovalent binding by the bispecific immunotoxin would not result in internalization. Against resting E+ T cells, the bispecific immunotoxin developed a minimal effect. On preactivating the same cells, using phorbol myristate acetate (PMA)/ionomycin on concanavalin A (ConA) or especially PHA, levels of CD26 were upregulated and the immunotoxin effectively inhibited the ability to provide help for B-cell Ig synthesis while leaving intact the CD4-CD26+ and CD4+CD26- populations; an effect observed both functionally and by phenotype. The bispecific antibody proved to be most effective at inhibiting a heterologous mixed leukocyte reaction. We propose that this reagent may form the basis for the rational design of toxins designed to modulate activated T cells from, or directed against, tissue grafts.

Antibodies, Monoclonal↗

PubMed1993

Direct association of adenosine deaminase with a T cell activation antigen, CD26.

CD26, the T cell activation molecule dipeptidyl peptidase IV (DPPIV), associates with a 43-kilodalton protein. Amino acid sequence analysis and immunoprecipitation studies demonstrated that this 43-kilodalton protein was adenosine deaminase (ADA). ADA was coexpressed with CD26 on the Jurkat T cell lines, and an in vitro binding assay showed that the binding was through the extracellular domain of CD26. ADA deficiency causes severe combined immunodeficiency disease (SCID) in humans. Thus, ADA and CD26 (DPPIV) interact on the T cell surface, and this interaction may provide a clue to the pathophysiology of SCID caused by ADA deficiency.

Adenosine Deaminase↗

PubMed1993

The costimulatory activity of the CD26 antigen requires dipeptidyl peptidase IV enzymatic activity.

T cells have been shown to express CD26, a known ectoenzyme with dipeptidyl peptidase IV (DPPIV; EC 3.4.14.5) activity in its extracellular domain. CD26 can also deliver a second costimulatory signal and contribute to T-cell activation. In an earlier study, we established CD26-transfected Jurkat T-cell lines and demonstrated that monoclonal antibody-mediated crosslinking of CD26 and CD3 induced interleukin 2 (IL-2) production. To determine the contribution of DPPIV enzymatic activity to the costimulatory activity of CD26, human CD26 cDNA was mutated so that active-site serine was replaced by alanine. The mutant CD26 antigen lacked DPPIV enzyme activity but still retained reactivity with three anti-CD26 monoclonal antibodies directed against distinct epitopes of CD26. After stimulation with a combination of anti-CD26 and anti-CD3 antibodies, wild-type CD26 (DPPIV+)-transfected Jurkat cells produced substantially more IL-2 than did mutant CD26 (DPPIV-) or CD26- control transfectants. Nevertheless, the mutant CD26-transfected cells still produced significantly more IL-2 than did CD26- control transfectants. These results suggest that DPPIV activity plays an important but not absolute role in the co-stimulatory activity of CD26 in this system. We also found that wild-type CD26 (DPPIV+) transfectants produced more IL-2 than mutant CD26 (DPPIV-)-transfected cells or CD26- control transfectants when triggered by stimuli not involving CD26, such as anti-CD3 and phorbol ester. These results suggest that the DPPIV activity of CD26 functions to augment the cellular responses of CD26-transfected Jurkat cells to external stimuli mediated by CD26 and/or the CD3/T-cell receptor complex, thus enhancing IL-2 production.

Antigens, Differentiation, T-Lymphocyte↗

PubMed1993

Stimulation of protein tyrosine phosphorylation in human B cells after ligation of the beta 1 integrin VLA-4.

B lymphocytes express several adhesion molecules that are involved in cell-cell and cell-extracellular matrix interactions. The alpha 4 beta 1 integrin VLA-4, expressed on pre-B and mature/activated B cells, mediates adhesion of these cells to its two ligands, VCAM-1 and fibronectin. Recent evidence suggests that VLA-4 is involved in T lymphocyte activation; however, relatively little is known of the role of VLA-4 in B cell differentiation. To begin to assess the potential involvement of VLA-4 in B cell activation, we have examined the effect of ligation of VLA-4 on protein tyrosine phosphorylation in B cells. We found that cross-linking of VLA-4 by either mAb or natural ligands (i.e., VCAM-1 and the FN-40 cleavage fragment of fibronectin) induced the tyrosine phosphorylation of a 110-kDa protein in a human pre-B cell line (Nalm-6), an EBV-transformed B cell line (SB), and normal tonsillar B cells. These findings suggest that VLA-4 can activate a tyrosine kinase in B cells and B cell lines. These signals may be involved in the subsequent differentiation of pre-B and mature B cells within specific microenvironments where VLA-4 mediated adhesion is operational.

Antigens, CD↗

PubMed1993

The 4F9 antigen is a member of the tetra spans transmembrane protein family and functions as an accessory molecule in T cell activation and adhesion.

In this report, we describe a 43- to 50-kDa protein, which may function as a costimulatory molecule for full activation of human T cells. This Ag, defined by a mouse monoclonal antibody (mAb) anti-4F9, is primarily distributed on "helper/inducer" or "memory" CD4+CD45RO+ subset. Like mAbs against many other accessory/costimulatory molecules, coimmobilization of anti-4F9 with anti-CD3 resulted in synergistic T cell proliferation. In addition, immobilized anti-4F9 on plastic plates induced T cell spreading characterized by the development of prominent dendritic processes. A cDNA encoding the 4F9 Ag was isolated from a cDNA library constructed from PHA/PMA-activated T cells using a COS cell expression system. The sequence of the cDNA and a homology search revealed that the 4F9 Ag was identical to R2, a molecule recently cloned by subtractive hybridization. The 4F9/R2 Ag belongs to a newly identified supergene family (tetra spans transmembrane protein family) characterized by four putative transmembrane domains which are highly conserved between the members of this family. Based upon the phenotypical and functional studies described here, we propose that the 4F9 Ag is an integral membrane protein which can transmit signals involved in T cell proliferation and adhesion. The preferential distribution of this molecule on the CD4+CD45RO+ subset of T cells may contribute to the distinct activation profile and functional repertoire of these cells.

Animals↗

PubMed1993

Direct demonstration of the CD27 molecule involved in the negative regulatory effect on T cell activation.

CD27 is a member of the nerve growth factor/tumor necrosis factor receptor family and appears to play an important role in the process of T cell activation. We have previously shown that perturbation of the CD27 molecule by anti-1A4 (CD27) mAb inhibits T cell proliferation induced by various stimuli. To further determine the molecular basis of this inhibition of T cell proliferation by anti-1A4 mAb, we have established CD27-transfectant lines. Introduction of the human CD27 cDNA to ovalbumin-specific I-Ad-restricted murine T cell hybridomas significantly reduced their antigen-specific IL-2 production. In addition, treatment of these human CD27 transfectants with an anti-CD27 mAb (anti-1A4) further reduced their IL-2 production. These results provide direct evidence that CD27 plays a crucial role in the process of T cell activation.

Animals↗

PubMed1993

Human CD4/CD45RA+ and CD4/CD45RA- T cell subsets express CD4-p56lck complexes, CD4-associated lipid kinases, TCR/CD3-p59fyn complexes, and share similar tyrosine kinase substrates.

T cell activation appears to be regulated by an interplay between protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPases). p56lck and p59fyn have been found to associate with CD4 and TCR-CD3 respectively. The CD45 family of transmembrane PTPases has been shown to be able to regulate the activities of these receptor-associated PTKs in vitro. In man, CD45 contains five different isoforms whose distribution defines subsets of T cells having distinct activation requirements and in vitro functions. Several groups have reported a physical interaction between distinct isoforms of CD45 and CD2, CD4, and the TCR-CD3 complex. Given the potential regulatory interaction between CD45 and PTKs in CD4+ subsets expressing different CD45 isoforms, we have examined CD4 associated and TCR-CD3- associated PTK activities, associated phosphatidyl inositol (PI) kinases and substrates of tyrosine phosphorylation in CD45RA+ and CD45RA- CD4+ T cell lines derived from peripheral blood. Both subsets express CD4-associated p56lck and TCR-CD3-associated p59fyn kinases which exhibit identical in vitro phosphorylation at the Y-394 and Y-420 autophosphorylation sites respectively. Further, both subsets exhibited PI kinases activity associated with CD4-p56lck. Consistent with these observations, anti-CD3 crosslinking induced the phosphorylation of a similar spectrum of intracellular substrates in these CD45RA+ and CD45RA- CD4+ T cell lines. These observations indicate that despite the possible interaction between CD45 isoforms and CD4 or TCR-CD3, the mere expression of the CD45RA isoform does not in and of itself alter the presence of receptor-associated kinases or their intracellular targets.

1-Phosphatidylinositol 4-Kinase↗

PubMed1993

Activation of human T cells through CD6: functional effects of a novel anti-CD6 monoclonal antibody and definition of four epitopes of the CD6 glycoprotein.

The CD6 glycoprotein is expressed primarily on lymphocytes and conveys co-activating signals to T cells, but its exact function and ligand(s) are unknown. A novel mAb, termed UMCD6, was demonstrated to recognize CD6 by immunoprecipitation, Western blotting, and reactivity with COS cells transfected with CD6 cDNA. UMCD6 was mitogenic for T cells and was strongly synergistic with phorbol ester in inducing T cell activation. UMCD6 enhanced the autologous mixed lymphocyte reaction as previously observed with another anti-CD6 mAb, anti-T12. The activating effects of UMCD6 were more striking than those of other anti-CD6 mAbs and encompassed all of the diverse stimulatory properties previously reported for other anti-CD6 reagents. However, neither UMCD6 nor other anti-CD6 antibodies alone or in combination with phorbol ester or IL-2 were able to induce thymocytes to proliferate. Stimulation by UMCD6 is dependent on accessory cell function in a manner not accounted for simply by antibody cross-linking. UMCD6 did not induce an increase in cytoplasmic free Ca2+, but the CD6 activation pathway appears to involve protein kinase C. UMCD6 and a panel of seven other anti-CD6 mAbs were used in a series of experiments to define four discrete epitopes of CD6 using the criteria of antibody cross-blocking, reactivity on reduced Western blots, and resistance to controlled V8 protease digestion. The functional mAbs UMCD6, 2H1, and anti-T12 each recognized a different epitope. Taken together, the results of these studies strongly reinforce the hypothesis that CD6 plays a significant and distinct role in T cell activation, and suggest that multiple regions of CD6 may be functionally active.

Antibodies, Monoclonal↗

PubMed1993

Depletion of the helper/inducer (memory) T cell subset using a bispecific antibody-toxin conjugate directed against CD4 and CD29.

We have developed a bispecific antibody that recognizes the CD4 and CD29 antigens simultaneously and that was examined for its ability to target CD4+CD29bright T cells. The premise for using bispecific antibody-toxin conjugates was that monovalent binding to one antigen would not result in internalization while binding through both antigens would predispose toward endocytosis and delivery of the toxin to the cell interior. In this study, we show that the bispecific antibody binds monovalently to CD4 and CD29 and bivalently to both antigens. Both monovalent and bivalent binding rendered the target cells sensitive to complement-mediated lysis, demonstrating that this effector modality cannot take advantage of the dual specificity of the antibody. Bivalent binding, however, allowed modulation of more than 60% of the bound antibody off the surface of CD4+CD29bright cells, which we further exploited to deliver a toxin moiety preferentially to CD4+CD29bright cells. Immunoconjugates incorporating blocked ricin (a ricin holotoxin that has its intrinsic galactose-binding sites blocked by chemically linked affinity ligands) preferentially killed CD4+CD29bright cells in vitro by a factor of 25 in comparison with killing of total CD4+ cells in functional assays. Assays on resting PBL demonstrated a similar specificity of the bispecific immunotoxin for CD4+CD29bright cells with a concomitant relative survival of CD4+CD29dim (CD45RA+). We demonstrated that the potency of the immunotoxin is not only a function of its affinity but also of its propensity to internalize, and that this property is influenced by the degree of bivalent binding. These results open up the possibility of engineering bispecific antibody toxin conjugates for use as therapeutic immunotoxins for selective removal of restricted T cell subsets.

Animals↗

PubMed1993

Protein kinase A-mediated phosphorylation of the T-cell surface antigen CD27.

CD27 is a T-cell surface antigen expressed on the majority of peripheral T cells and belongs to a newly defined receptor family including the low-affinity nerve growth factor receptor, tumour necrosis factor (TNF) receptors, the B-cell activation antigen CD40, and the Fas antigen. Although the function of CD27 has not been defined, several experimental observations support the notion that this molecule plays an important role in the process of T-cell activation. In this paper, we have demonstrated that a rapid hyperphosphorylation of CD27 is induced by a cyclic AMP-inducing agent, forskolin, and a membrane-permeable cAMP analogue, 8-bromo-cAMP, as well as phorbol 12-myristate 13-acetate (PMA). In addition, increased phosphorylation of CD27 in T-cell activation either via CD2 or CD3 pathways was strongly suppressed by a cyclic nucleotide-dependent kinase inhibitor, H-8, but only slightly by a protein kinase C inhibitor, staurosporine. These results suggest that protein kinase A might be a key kinase responsible for CD27 phosphorylation in the process of T-cell activation. CD27 is the first T-cell surface antigen demonstrated to be phosphorylated by the cyclic AMP-protein kinase A-mediated pathway.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1992

Interleukin-11 promotes accessory cell-dependent B-cell differentiation in humans.

Interleukin-11 (IL-11) is a recently described stromal-derived cytokine that supports the growth of an IL-6-dependent murine plasmacytoma line in the presence of antibody to IL-6 and appears to act in a manner similar to IL-6 on hematopoietic stem cells. Because IL-6 is known to promote differentiation of normal human B cells, the role of IL-11 on B-cell differentiation in vitro was characterized. IL-11 does not result in significantly increased DNA synthesis or Ig secretion by purified B cells alone or B cells cultured with Staphylococcus Cowan I, a T-cell-independent B-cell mitogen. In contrast, purified B cells cultured in the presence of pokeweed mitogen (PWM), irradiated T cells, and monocytes show increased DNA synthesis at day 3 and increased IgG and IgM secretion at day 7 of culture; addition of IL-11 further augments Ig secretion without change in DNA synthesis, an effect that can only be partially blocked by monoclonal antibody to IL-6. Similar experiments confirmed that increased IgG secretion was demonstrable when either IL-11 or IL-6 was added to B cells + CD4+/45RA- T cells + monocytes + PWM; in contrast, Ig secretion was low and equivalent when CD4+/45RA+ T cells were cultured with B cells+monocytes+PWM with or without IL-6 or IL-11. Neither IL-6 nor IL-11 could significantly increase phytohemagglutinin (PHA)-induced DNA synthesis by CD4+/45RA- or CD4+/45RA+ T cells. Although PWM or IL-11 induced IL-6 mRNA expression in both CD4+/45RA- T cells and monocytes, in neither cell did IL-11 increase IL-6 mRNA expression over that noted to PWM alone. These observations support the view that IL-11 promotes differentiation of human B lymphocytes only in the presence of accessory T cells and monocytes and that a minor component of this effect may be through stimulation of IL-6 production by CD4+/45RA- T cells and monocytes.

Actins↗

PubMed1992

CD27, a member of the nerve growth factor receptor family, is preferentially expressed on CD45RA+ CD4 T cell clones and involved in distinct immunoregulatory functions.

CD27 is a disulfide-linked 120-kDa homodimer expressed on the majority of peripheral T cells at variable density that belongs to the recently defined nerve growth factor receptor family. mAb reactive with CD27 can either enhance or inhibit T cell activation, suggesting a crucial role in the process of T cell activation. We now show that CD27 is preferentially expressed on the CD45RA+CD45RO-CD29low subset of CD4 cells. CD27 expression on this subset is maintained for a prolonged period in culture after PHA activation. In contrast, CD45RA-CD45RO(+)-CD29high subset of CD4 cells express very low level of CD27, and its expression is lost within 2 wk after PHA activation. To further analyze the differential expression of CD27 on these reciprocal subsets of CD4 cells, we developed T cell clones by stimulating isolated CD4+CD45RA+ and CD4+CD45RO+ populations with PHA. T cell clones derived from cells originally CD45RA+ retained both CD45RA and CD27 expression, whereas T cell clones derived from cells originally CD45RO+ were CD45RA- and CD27-. In functional assays, IL-4 production could only be induced in CD45RA-CD27- CD4 clones by stimulation with PMA and ionomycin. Four of six CD45RA+ CD4 clones had suppressor activity in PWM-driven IgG synthesis, whereas five of six CD45RA- CD4 clones had helper activity. Of interest, the suppressor activity of CD45RA+CD27+ clones was partially blocked by pretreatment with anti-CD27 mAb (1A4). Anti-1A4 pretreatment of these T cell clones resulted in elevation of intracellular cAMP levels. Thus, CD27 appears to play a role in the function of CD45RA+CD27+ CD4 cells, and may be involved in suppressor activity of these cells at least in part via its effects on cAMP production.

Antigens, CD↗

PubMed1992

Participation of the CD27 antigen in the regulation of IL-2-activated human natural killer cells.

The CD27 Ag is expressed by the majority of resting T lymphocytes and appears to play a crucial role in T cell activation. We found that some resting peripheral blood NK cells also express CD27. Furthermore, CD27 expression was up-regulated on NK cells stimulated by IL-2. The cytolytic activity of IL-2-activated, but not resting, NK cells was inhibited by an anti-CD27 mAb (anti-1A4). However, anti-1A4 did not affect conjugate formation between IL-2-activated NK cells and tumor cell targets. In contrast, anti-1A4 inhibited CD2-mediated calcium mobilization and the serine esterase activity of NK cell granules. These inhibitory effects could be mediated in part by increase in intracellular cAMP levels induced by anti-1A4. Our results suggest that the CD27 Ag plays an important role in the regulation of activated NK cells.

Antigens, CD↗

PubMed1992

Cloning and functional expression of the T cell activation antigen CD26.

A cDNA encoding the T cell activation Ag CD26 was isolated from human PHA-activated T cells by using an expression cloning method. The nucleotide sequence obtained predicts a protein of 766 amino acids of type II membrane topology, with six amino acids in the cytoplasmic region. The predicted amino acid sequence of the Ag was 85% homologous to that of the dipeptidyl peptidase IV enzyme isolated from rat liver. Derivatives of the human leukemic T cell line Jurkat transfected with a CD26 expression plasmid were established. Characterization of the CD26 Ag expressed by the transfected Jurkat cells revealed that the Ag could be immunoprecipitated as a 110-kDa molecule similar to that found on peripheral blood T cells and that the Ag had dipeptidyl peptidase IV activity. Functional analysis of these Jurkat transfectants showed that cross-linking of the CD26 and CD3 Ag with their respective antibodies resulted in enhanced intracellular calcium mobilization and IL-2 production. These results provide direct evidence that the CD26 Ag plays a role in T cell activation.

Amino Acid Sequence↗