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T Kobata

Publications and source records attributed to T Kobata.

At least 73 records · Page 4Linked to original sources

CD27/CD70 interaction directly induces natural killer cell killing activity.

The CD27 molecule is expressed on a portion of natural killer (NK) cells as well as T and B cells. To provide the functional capacity of CD27 molecule on NK cells, we here highly purified CD3- CD56+ NK cells by flow cytometry (purity > 98%), and investigated their NK cell activity via CD27/CD70 interaction using a CD70-transfectant by a 4 h 51Cr-release assay. The enhancement of NK activity by purified NK cells in the presence of interleukin-2 (IL-2) or interleukin-12 (IL-12) against CD70/Nalm-6 was not recognized as compared to against mock/Nalm-6. However, after a coculture with the fixed CD70/300-19, the purified NK cells increased the NK cell activity against K562, the value being 10 to 20% higher than coculture with the mock/300-19 in the presence of IL-2 or IL-12. The enhancement of NK activity was blocked by the addition of anti-CD70 monoclonal antibody (mAb). In addition, conjugation of NK cells to the target was increased by coculture with the CD70/300-19 without increased expression of adhesion molecules. In the parallel experiment, there was no increase in the killing capacity of NK cells. These results strongly show that CD27/CD70 interaction directly enhances NK activity in the presence of IL-2 or IL-12 by increasing the effector and target conjugate formation, indicating that CD27/CD70 interaction plays an important role in the cytotoxic function of NK cells.

Antigens, CD↗

Novel mechanisms of selective apoptosis in synovial T cells of patients with rheumatoid arthritis.

OBJECTIVE: To analyze whether T cells infiltrating the synovium of patients with rheumatoid arthritis (RA) express functional Fas antigen. METHODS: Mononuclear T cells, mainly from synovial tissues, synovial fluids (SF), and peripheral blood mononuclear cells (PBMC) from 14 patients with RA and 5 with osteoarthritis (OA), were treated with anti-Fas monoclonal antibody (Mab) (CH11) for 24 h in vitro. Cell viability and DNA fragmentation were examined. The expression of Fas antigen, Fas ligand, and T cell subpopulations was examined using flow cytometry and reverse transcription polymerase chain reaction. RESULTS: More than 50% of T cells from synovial tissue and SF of patients with RA underwent apoptosis, whereas no effect was observed in PBMC from RA or PBMC and synovial T cells from OA, suggesting that functional Fas antigens are specifically expressed on synovial T cells. Flow cytometric analysis demonstrated higher expression of Fas antigen in T cells from RA synovium than from PBMC. The T cell subpopulations susceptible to anti-Fas Mab were mainly CD45RO+ and CD4 or CD8 single positive T cells, indicating that activated mature T cells express functional Fas antigen. Fas ligand was overexpressed only in synovial nonadherent cells in RA at the level of mRNA, whereas T cells account for more than 60% of the total, but not in OA. CONCLUSION: These findings suggest the majority of activated T cells infiltrating the synovium express functional Fas antigen and Fas ligand specifically in patients with RA but not OA. This phenomenon may provide a clue to understanding the pathogenesis of RA.

Adult↗

CD27-CD70 interactions regulate B-cell activation by T cells.

CD27, a member of the tumor necrosis factor (TNF) receptor family, binds to its ligand CD70, a member of the TNF family, and subsequently induces T-cell costimulation and B-cell activation. CD27 is expressed on resting T and B cells, whereas CD70 is expressed on activated T and B cells. Utilizing transfected murine pre-B-cell lines expressing human CD27 or CD70, we have examined the effect of such transfectant cells on human B-cell IgG production and B-cell proliferation. We show that the addition of CD27-transfected cells to a T-cell-dependent, pokeweed mitogen-driven B-cell IgG synthesis system resulted in marked inhibition of IgG production, whereas the addition of CD70-transfected cells enhanced IgG production. The inhibition and enhancement of pokeweed mitogen-driven IgG production by CD27 and CD70 transfectants were abrogated by pretreatment with anti-CD27 and anti-CD70 monoclonal antibodies, respectively. In contrast, little or no inhibition of IgG production and B-cell proliferation was noted with CD27-transfected cells or either anti-CD27 or CD70 monoclonal antibody in a T-cell-independent Staphylococcus aureus/interleukin 2-driven B-cell activation system. In this same system CD70-transfected cells enhanced B-cell IgG production and B-cell proliferation, and this enhancement could be gradually abrogated by addition of increasing numbers of CD27-transfected cells. These results clearly demonstrate that interactions among subsets of T cells expressing CD27 and CD70 play a key role in regulating B-cell activation and immunoglobulin synthesis.

Antigens, CD↗

Direct cellular communications between CD45R0 and CD45RA T cell subsets via CD27/CD70.

The engagement of CD27 with its ligand CD70 is considered to play an important role in T cell costimulation. In the present study, we investigated both the kinetics of CD70 expression and the contribution of its interaction with CD27 in T cell immune responses. CD70 was found to be expressed almost equally on both activated CD4 and CD8 T cells. On subsets of CD4 T cells, however, CD70 expression was induced preferentially on the CD45R0 T cell population after activation, whereas its expression was not noted on CD45RA T cells for almost 2 wk following activation. In long-term culture with media containing T cell growth factor (TCGF) and rIL-2, the expression of CD70 was increased markedly on CD45R0 T cells and minimally expressed on CD45RA T cells. In addition, strong surface expression of CD70 was observed on T cell clones originally derived from CD45R0+ CD4 T cells, whereas T cell clones originally derived from CD45RA+ CD4 T cells showed lower levels of expression. The addition of irradiated, activated CD45R0 T cells to CD45RA T cells caused a down-regulation of CD27 expression and an up-regulation of CD25 expression. These changes were blocked by addition of the anti-CD70 mAb, suggesting that direct contact between CD45R0 T cells and CD45RA T cells via CD27/CD70 occurred, leading to the activation of CD45RA T cells as measured by CD25 expression. These observations strongly support the notion that the engagement of CD27 plays an important regulatory role in the communication of subsets of CD45R0 and CD45RA T cells.

Antigens, CD↗

CD27/CD70 interaction directly drives B cell IgG and IgM synthesis.

CD27 is a T cell activation antigen expressed on a majority of peripheral blood T cells. CD27 is also expressed on a subpopulation of human B cells, and it is reported that CD27+ B cells secrete both IgG and IgM. CD70, a ligand for CD27, is expressed on activated T and B cells, suggesting an interaction between T and B cells via CD27/CD70 ligation. Here, we analyze B cell immunoglobulin synthesis using a CD70 transfectant and present functional data showing that B cells secrete large amounts of IgG and IgM as a result of the CD27/CD70 interaction. A flow cytometric analysis showed that CD27 expression was increased and CD70 was expressed on tonsillar and peripheral blood B cells after activation with Staphylococcus aureus Cowan strain (SAC) plus interleukin (IL-2). In addition, the proliferation of B cells was enhanced mildly by the addition of CD70 transfectant, and its proliferation was blocked by anti-CD70 mAb. More importantly, the CD70 transfectant enhanced IgG and IgM production by purified B cells greatly in the presence of SAC plus IL-2. The enhancement was completely blocked by the addition of either anti-CD70 mAb or anti-CD27 mAb. Strongly suggesting that the interaction of CD27 with its ligand, CD70, on B cells plays an important role in B cell growth and differentiation to produce IgG and IgM.

Adult↗

CD27 is a signal-transducing molecule involved in CD45RA+ naive T cell costimulation.

CD27 is a 120-kDa transmembrane homodimeric molecule expressed on the majority of T cells, B cells, and NK cells that belongs to the TNFR/nerve growth factor receptor family. The interaction between CD27 and its ligand, CD70, is thought to play an important role in T cell activation. In this paper we have examined the signal-transducing potential of CD27 in T cell costimulation. Anti-CD27 mAb, anti-1A4, induced substantial proliferation of peripheral blood T cells in the presence of a suboptimal dose of PMA, phytohemagglutinin, anti-CD2, or anti-CD3 together with a second Ab to cross-link the CD27 molecule. This T cell proliferation was also observed by using CD70 transfectant cells. CD27 cross-linking maximally induced proliferation of CD45RA+CD4 T cells but only slightly induced proliferation of CD45RO+CD4 T cells. CD27-mediated T cell proliferation did not seem to be dependent on the IL-2/IL-2R system because no detectable level of IL-2 was secreted, and only a partial inhibition was observed with anti-IL-2 and anti-IL-2R Abs. Furthermore, an increase in intracellular Ca2+ was observed in PMA-treated T cells when the CD27 molecule was cross-linked. More importantly, CD27 ligation induced protein tyrosine phosphorylation, especially 70 kDa of cellular substrate, including ZAP-70, in T cells. Herbimycin A, a protein tyrosine kinase inhibitor, and staurosporine, a protein kinase C inhibitor, blocked T cell proliferation induced by CD27 ligation, suggesting the possibility that the activation of protein tyrosine kinase and protein kinase C is required for CD27-mediated T cell costimulation. These results clearly demonstrate that the CD27/CD70 interaction induces costimulatory signals in T cells, especially CD45RA+ naive T cells, indicating that CD27 serves as a T cell signal-transducing molecule.

Base Sequence↗

Differential regulation of CD27 expression on subsets of CD4 T cells.

Our earlier studies showed that although CD27 was stably expressed on the CD45RA(+)-CD45RO-CD29low subset of CD4 T cells, its expression on the CD45RA-CD45RO+CD29high subset of CD4 T cells was gradually lost within 3 weeks after PHA activation. In the present study, we further determined the mechanisms by which the CD27 expression was differentially regulated on the subsets of CD4 T cells. We showed that disappearance of CD27 from the surface of the CD45RA-CD45RO+ subset of CD4 T cells was not solely due to the shedding of the CD27 molecule from the cell surface since the release of a soluble form of the CD27 molecule from the CD45RO+ CD4 T cells was consistently less than that from CD45RA+ CD4 T cells. Although the surface CD27 expression was undetectable on long-term cultured T cell lines originally derived from CD45RO+ CD4 T cells, some of these cells still expressed intracellular CD27 and CD27 mRNA. Moreover, restimulation could not induce CD27 expression on such cells. Further analysis of CD27 protein and mRNA expression at a clonal level showed that cloned cells derived from CD45RO+ CD4 T cells having lost cell surface expression of CD27 were of two types: one expressed intracellular CD27 mRNA and protein whereas the second lacked both intracellular CD27 mRNA and protein.

Blotting, Northern↗

Role of CD27 in T cell immune response. Analysis by recombinant soluble CD27.

CD27 is a disulfide-linked 120-kDa transmembrane glycoprotein expressed on the majority of T cells, B cells, and NK cells; it has homology to a family of molecules that includes the receptors for nerve growth factor and TNF. Previous studies strongly suggest that the CD27 molecule plays a key role in the process of T cell activation. To further determine its role in T cell activation, a recombinant soluble molecule composing only the extracellular domain of CD27 was produced by transfection of Chinese hamster ovary cells. We have defined the binding properties of recombinant soluble CD27 (rsCD27) to CD27 ligand (CD27L) cDNA transfected NIH 3T3 cells and have determined its functional effects on in vitro T cell activation as well as on PWM-driven B cell IgG synthesis. rsCD27 bound specifically to CD27L and the binding was inhibited by one of our anti-CD27 mAbs, anti-1A4, suggesting that the 1A4 epitope of CD27 plays a role in the binding to CD27L. Functionally, rsCD27 inhibited T cell proliferation induced by various stimuli, such as PHA, tetanus toxoid, and anti-CD2, as well as PWM-driven B cell IgG synthesis, similar to the effects of adding anti-1A4. Determination of CD27L expression showed that CD27L mRNA is induced rapidly on activated T and B cells. Taken together, these results provide direct evidence that CD27-CD27L interaction plays a critical role in T cell activation as well as in T cell-dependent B cell IgG synthesis, suggesting that the CD27-CD27L interaction may constitute a component of the T cell-T cell or T cell-B cell interaction seen after activation with Ag or mitogen.

Antibody Formation↗

3H11, a unique cell surface molecule involved in the function of the CD45RA+ subset of CD4+ cells.

We have developed a mAb anti-3H11 by immunizing mice with a T cell line derived from the Callithrix jacchus (common marmoset). Anti-3H11 is reactive with approximately 48% of unfractionated T cells, 62% of CD4+ cells and 39% of CD8+ cells. Among CD4 cells, anti-3H11 preferentially reacts with the CD45RA+ T cell subset. The majority of helper activity for pokeweed mitogen (PWM)-driven B cell IgG synthesis and T cell response to recall antigen such as tetanus toxoid was found within the 3H11-CD4 cell population, whereas anti-3H11+CD4+ cells provided poor helper function for PWM-driven B cell IgG synthesis and were more responsive to concanavalin A and autologous mixed lymphocyte reaction. Biochemical characterization showed that anti-3H11 precipitated a single protein band with a relative molecular weight of 32,000 from 125I-surface labeled cell lysate. Biochemical, phenotypic and functional studies revealed that the 3H11 molecule appeared to be different from previously established molecules on the T cell surface. Interestingly, addition of anti-3H11 to the combination of CD4 and B cells in the presence of CD8 cells but not to the combination of CD4 and B cells resulted in enhancement of the suppression of PWM-driven B cell IgG synthesis. Moreover, anti-3H11 had a co-mitogenic effect on T cells via the CD2 and CD3 pathways, and this co-mitogenic activity is restricted to the CD45RA+ T cells. Taken together, our results show that the 3H11 molecule is a novel antigen which may play an important role in the activation and function of the CD45RA+ subset of T cells.

Animals↗

UV irradiation can induce in vitro clonal anergy in alloreactive cytotoxic T lymphocytes.

The alloreactive cytotoxic T lymphocytes (CTL) were generated by coculturing peripheral blood mononuclear cells (PBMC) with allogeneic Sa cells (an Epstein-Barr virus [EBV]-transformed B-cell line). The CTL did not proliferate in response to UV-B-irradiated Sa cells unless exogenous interleukin-2 (IL-2) was present, although they could kill the UV-B-irradiated Sa cells. The results indicate that UV-B-irradiated Sa cells do not provide sufficient signals for the proliferation of the CTL while they can be recognized by CTL and induce high-affinity IL-2 receptor (IL-2R) expression on them. The alloreactive CTL could be rendered anergic by previous exposure to UV-B-irradiated Sa cells. The alloreactive CTL previously stimulated with UV-B-irradiated Sa cells failed to proliferate in response to nontreated Sa cells. Proliferation of the anergic CTL could not be restored by Sa cells and exogenous IL-2 but by the combination of phorbol 12-myristate 13-acetate (PMA) and calcium ionophore (A23187). The anergic CTL showed a considerably low cytotoxic activity against Sa target cells. The expression of TCR on the anergic CTL was downregulated while expression of high-affinity IL-2R was upregulated. Their CD28 and CD8 expression were unchanged. In addition, the proliferative response and cytotoxicity of the anergic CTL to Sa cells could be restored after the cells had been rested for 7 days to allow reexpression of TCR. These results suggest that downregulation of T-cell receptor (TCR) and impairment in the post-IL-2/IL-2R signaling pathway are relevant to the clonal anergy induced in the alloreactive CTL by stimulation of UV-B-irradiated Sa cells.

Antigens, CD↗

Ultraviolet irradiation inhibits killer-target cell interaction.

The effects of ultraviolet (UV) irradiation on cell-mediated cytolysis were examined in order to clarify the inhibitory mechanisms of allosensitization by UV irradiation. UV-B-irradiated target cells (Sa; an Epstein-Barr virus-transformed B cell line) exhibited more resistance against alloreactive cytotoxic T lymphocytes (CTL) than mitomycin C (MMC)-treated target cells. In the conjugate formation assay, UV-B-irradiated target cells showed a considerably lower binding to alloreactive CTL than MMC-treated target cells. UV-B irradiation induced a reduction of HLA-class I, -DR, CD54 (ICAM-1) and CD58 (LFA-3) expression on target cells. However, it does not seem to contribute to the inhibition of cell adhesion induced by UV-B irradiation because a similar reduction of cell surface antigens was observed in MMC-treated target cells. Number of cells capped with anti-HLA-class I, -DR, CD54 or CD58 monoclonal antibody were markedly reduced by UV-B irradiation compared to that by MMC treatment. These findings suggest the possibility that the inhibition of cell adhesion between UV-B-irradiated Sa target cells and alloreactive CTL is due to the impaired mobility of cell surface antigens which will affect the early process of cell-mediated cytolysis.

Cell Communication↗

Extrathymic origin of V gamma 1/V delta 6 T cells in the skin.

The dendritic epidermal cells (dEC) from young (8-week-old) athymic mice were found to express mRNA for gamma/delta T cell receptors (TcR). The mRNA found in the dEC from athymic mice was expressed only for V gamma 1-J gamma 4-C gamma 4 and V delta 6-J delta 1-C delta with both chains having productive rearrangements and junctional diversity. On the other hand, the dEC from euthymic mice carried V gamma 5-J gamma 1-C gamma 1 and V delta 1-J delta 2-C delta in addition to the V gamma 1/V delta 6 subset found in athymic mice. Therefore, this V gamma 1/V delta 6 subset, which has been implicated in the murine gamma/delta T cell responses to mycobacterial antigens and self heat-shock proteins, is the product of extrathymic maturation in the dEC from both athymic and euthymic mice.

Animals↗

Reciprocal T cell responses in the liver and thymus of mice injected with syngeneic tumor cells.

We investigated the T cell responses in various tissues, especially in the liver and thymus, of mice injected with syngeneic tumors. This study was undertaken since recent evidence indicated that the liver is one of the important immune organs for T cell proliferation. When C3H/He mice were intraperitoneally injected with mitomycin-treated syngeneic MH134 tumors (1 x 10(7)/mouse), a transient increase of liver mononuclear cells (MNC) was induced, showing a peak at Day 4 after injection. Histological study of such liver showed a sinusoidal dilatation and an accumulation of MNC in the sinusoids. The most predominant MNC induced were double negative (CD4-8-) alpha beta T cells and gamma delta T cells. These gamma delta T cells varied, showing unique time-kinetics. Despite a continuous increase of whole liver MNC and alpha beta T cells, the proportion of gamma delta T cells in the liver decreased beginning 4 days after injection. In contrast with the response in the liver, a striking decrease in the cell number of thymocytes was induced after tumor injection, showing a basal level at Day 6. This hypocellularity in the thymus appears to be an inverted response of the lymphocytosis in the liver. At this time, a corresponding decrease in the proportion of double positive (CD4+8+) T cells was always seen in the thymus. Analysis of cell proliferative response showed that the increase of liver MNC after tumor injection was accompanied by augmented proliferation, whereas the decrease of thymocytes was accompanied by depressed proliferation. The present results indicate that there exists a unique, reciprocal response of T lymphocytes between the liver and thymus, and that the presence of tumor appears to stimulate T cell response in the liver but alternatively inactivates such response in the thymus.

Animals↗

Predominant appearance of gamma/delta T lymphocytes in the liver of mice after birth.

gamma/delta T lymphocytes residing in the liver of mice were systematically characterized with respect to their age-related variation, phenotype and V gene segment usage of gamma/delta T cell receptor (TcR). Previous human and murine studies have shown that a high proportion of gamma/delta T cells reside in the liver and that such liver gamma/delta T cells have lymphoblastic morphology and can spontaneously proliferate in vitro. In the present study, a predominant appearance of gamma/delta T cells (up to 23% among CD3+ cells) in the liver was confirmed in 4-week old mice of various strains. gamma/delta T cells in the liver preferentially co-expressed CD8 antigens, whereas the vast majority of gamma/delta T cells in the spleen lacked the CD8 antigens. The identification of gamma/delta T cells in various lymphoid and non-lymphoid organs also revealed the liver to be one of the organs where gamma/delta T cell are most abundant. The level of such liver gamma/delta T cells showed a clear age-related variation. In the fetal stage and just after birth, gamma/delta T cells were not detectable in the liver (less than 0.2%). However, a significantly higher percentage of gamma/delta T cells among both the total population of mononuclear cells and CD3+ cells was detected in the liver of young 2- to 8-week-old mice; this percentage subsequently declined. As the total number of liver mononuclear cells increased in aged mice, the absolute number of liver gamma/delta T cells also increased as a function of age. V gene segment usage analysis by the polymerase chain reaction method demonstrated that V gamma 1 or V gamma 2/V delta 6 were preferentially used by liver gamma/delta T cells. The age-related increase of gamma/delta T cells was more prominent in the liver of athymic nude mice, and such gamma/delta T cells highly co-expressed the CD8 antigens and also utilized the V gamma 1 or V gamma 2/V delta 6 for gamma/delta Tcr. The predominant appearance of unique gamma/delta T cells in the liver, which was inversely related to the existence of the thymus, indicates that these gamma/delta T cells may differentiate extrathymically in the liver.

Age Factors↗

Expression and function of a 90-kilodalton homodimeric molecule (10D1 antigen) on human thymocytes.

The 10D1 Ag is a 90-kDa homodimeric molecule specifically expressed on a subpopulation of human T cells, and is involved in an alternative pathway of T cell activation. In the present study, we have examined the expression and function of the 10D1 Ag on human thymocytes. Three-color FMF analysis showed that the 10D1 Ag was highly expressed on minor but distinct subpopulations of double-negative and CD4 single-positive thymocytes, and weakly on a part of double-positive thymocytes, but not on CD8 single-positive thymocytes. In double-negative thymocytes, the vast majority of 10D1+ cells were immature thymocytes of CD7+2+3- phenotype. Interestingly, 10D1 mAb could induce the proliferation of CD4 single-positive thymocytes in the presence of goat anti-mouse Ig to cross-link the 10D1 Ag. The treatment of thymocytes with OKT4 mAb plus C but not with OKT8 mAb plus C totally abrogated the proliferative response induced by 10D1 mAb, indicating that the 10D1-responsible thymocytes were of CD4+8- phenotype. This 10D1 mAb-induced thymocyte proliferation was perfectly dependent on the endogenous IL-2/IL-2R system since a complete inhibition was observed with anti-IL-2 and anti-IL-2R mAb. The proliferating CD4 single positive thymocytes predominantly expressed the IL-2R alpha (p55) but not a detectable level of the IL-2R beta (p75). These results indicate that, although the 10D1 Ag can be detected on the CD7+2+3-4-8- thymocytes, its functional expression is restricted to a minor more mature CD4+ thymocyte population as well as in peripheral blood T cells, and the implications of these findings are discussed.

Antibodies, Monoclonal↗

A novel homodimeric molecule involved in human T cell activation.

A mAb, 10D1, was obtained by fusing spleen cells from BALB/c mice immunized with a CD3/TCR- human T cell line, P12/ichikawa, to mouse myeloma cells, P3X63-Ag8-653. 10D1 mAb is specific for T cells in that it reacted with all the T cell lines tested, but not with B or myeloid cell lines. A small fraction of normal peripheral blood T cells, preferentially CD4+, was also reactive with 10D1 mAb. Biochemical studies revealed that 10D1 mAb recognizes a disulfide-linked homodimeric molecule composed of 90-kDa polypeptide. 10D1 mAb induced a substantial proliferation of peripheral blood T cells when cross-linked with goat anti-mouse Ig antibody. The elimination of CD4+ cells totally abrogated the proliferative response induced by 10D1 mAb, whereas the elimination of CD8+ cells rather enhanced it. The proliferative response of peripheral blood T cells induced by 10D1 mAb was almost completely inhibited after modulation of the CD3/TCR complex with anti-CD3 mAb. In addition, a prompt increase in intracellular [Ca2+] was observed in a CD3+ T cell line, Jurkat but not in its surface CD3- mutant when 10D1 mAb was added. These results indicate that the 10D1 molecule is involved in a novel pathway of human CD4+ T cell activation, which is associated with the CD3/TCR-mediated pathway.

Antibodies, Monoclonal↗

Thy-1-positive dendritic epidermal cells contain a killer protein perforin.

The killer cell characteristics of Thy-1-positive dendritic epidermal cells (Thy-1+ DEC) were examined. Four Thy-1+ DEC clones which were established from athymic nude mice exhibited spontaneous or lectin-redirectable cytotoxic activity against some murine tumor cell lines in a 4 h 51Cr-release assay. A colorimetric assay for benzyloxycarbonyl-L-lysine-thiobenzyl ester esterase revealed a strong serine esterase activity expressed in all cell clones. In addition, Northern blot analysis using a murine perforin cDNA probe revealed that all four Thy-1+ DEC clones expressed abundant mRNA for perforin, as do most killer T cells. More importantly, immunocytochemical staining with an anti-perforin monoclonal antibody revealed that not only all four Thy-1+ DEC clones but also a part of freshly isolated Thy-1+ DEC from normal and nude mice contained perforin. These results demonstrate that Thy-1+ DEC exhibit typical killer cell characteristics in vitro and in vivo. These data also suggest that Thy-1+ DEC may play a cytotoxic role in protecting the integrity of skin from infection or neoplastic transformation.

Animals↗