scholarly journals Selection of rabbit CD4- CD8- T cell receptor-gamma/delta cells by in vitro transformation with human T lymphotropic virus-I.

1993 ◽  
Vol 178 (4) ◽  
pp. 1337-1345 ◽  
Author(s):  
S Sawasdikosol ◽  
B F Hague ◽  
T M Zhao ◽  
F S Bowers ◽  
R M Simpson ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Lines ◽  
Cell Receptor ◽  
Gamma Delta ◽  
T Lymphotropic Virus ◽  
T Cell Lines ◽  
Delta Cells ◽  
Selection Of ◽  
Gamma Delta Cells

In vitro transformation of rabbit peripheral blood mononuclear cells (PBMC) with human T lymphotropic virus-I (HTLV)-infected human or rabbit cells resulted in CD4- CD8- cell lines, some of which caused acute leukemia when injected into rabbits. Structural analyses of the proviruses from cell lines with diverse pathogenic effects provided no clear correlation with lethality. The rabbit lines were provisionally designated T cells because they express interleukin 2R (IL-2R) and CD5 and lack surface immunoglobulin, but none express functional T cell receptor (TCR) alpha or beta transcripts. A more detailed characterization of the HTLV-I-infected cells was required to determine cell lineage and its potential influence on pathogenic consequences. Probes for rabbit TCR gamma and delta genes were derived and used to detect gamma and delta TCR RNA transcripts, identifying the in vitro transformed lines as gamma/delta T cells. CD4+ and CD8+ lines were derived from PBMC of HTLV-I-infected rabbits and CD4+ TCR-alpha/beta HTLV-I lines were derived from rabbit thymus, eliminating the possibility that the HTLV-I isolates used here transform only CD4- CD8- TCR-gamma/delta cells. The percentage of gamma/delta cells in rabbit PBMC is relatively high (23% in adult rabbits); this with diminution of CD4+ and CD8+ cells in IL-2-supplemented PBMC or thymocyte cultures may account for selection of rabbit HTLV-I-infected gamma/delta T cell lines in vitro. The availability of well-characterized T cell lines with diverse in vivo effects in the rabbit HTLV-I disease model allows evaluation of roles played by cell type in HTLV-I-mediated disease.

scholarly journals Structure and specificity of T cell receptor gamma/delta on major histocompatibility complex antigen-specific CD3+, CD4-, CD8- T lymphocytes.

1988 ◽  
Vol 168 (5) ◽  
pp. 1899-1916 ◽  
Author(s):  
J A Bluestone ◽  
R Q Cron ◽  
M Cotterman ◽  
B A Houlden ◽  
L A Matis
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Line ◽  
Gene Segment ◽  
Cell Receptor ◽  
Gamma Delta ◽  
Human T Cells ◽  
T Cell Lines ◽  
Gamma Delta T Cell ◽  
Delta Cells

Analyses of TCR-bearing murine and human T cells have defined a unique subpopulation of T cells that express the TCR-gamma/delta proteins. The specificity of TCR-gamma/delta T cells and their role in the immune response have not yet been elucidated. Here we examine alloreactive TCR-gamma/delta T cell lines and clones that recognize MHC-encoded antigens. A BALB/c nu/nu (H-2d)-derived H-2k specific T cell line and derived clones were both cytolytic and released lymphokines after recognition of a non-classical H-2 antigen encoded in the TL region of the MHC. These cells expressed the V gamma 2/C gamma 1 protein in association with a TCR-delta gene product encoded by a Va gene segment rearranged to two D delta and one J delta variable elements. A second MHC-specific B10 nu/nu (H-2b) TCR-gamma/delta T cell line appeared to recognize a classical H-2D-encoded MHC molecule and expressed a distinct V gamma/C gamma 4-encoded protein. These data suggest that many TCR-gamma/delta-expressing T cells may recognize MHC-linked antigens encoded within distinct subregions of the MHC. The role of MHC-specific TCR-gamma/delta cells in immune responses and their immunological significance are discussed.

scholarly journals A role for interleukin 4 in the differentiation of mature T cell receptor gamma/delta + cells from human intrathymic T cell precursors.

1990 ◽  
Vol 172 (2) ◽  
pp. 439-446 ◽  
Author(s):  
A Bárcena ◽  
M L Toribio ◽  
L Pezzi ◽  
C Martínez
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Critical Role ◽  
Cell Receptor ◽  
Interleukin 4 ◽  
Gamma Delta ◽  
Consistent Finding ◽  
Delta Cells ◽  
Gamma Delta Cells

We have analyzed the effect of human recombinant interleukin 4 (rIL-4) on the growth and differentiation of human intrathymic pre-T cells (CD7+2+1-3-4-8-). We describe that this population of T cell precursors proliferates in response to rIL-4 (in the absence of mitogens or other stimulatory signals) in a dose-dependent way. The IL-4-induced proliferation is independent of the IL-2 pathway, as it cannot be inhibited with an anti-IL-2 receptor alpha chain antibody. In our culture conditions, rIL-4 also promotes the differentiation of pre-T cells into phenotypically mature T cells. Although both CD3/T cell receptor (TCR)-alpha/beta + and CD3-gamma/delta + T cells were obtained, the preferential differentiation into TCR-gamma/delta + cells was a consistent finding. These results suggest that, in addition to IL-2, IL-4 plays a critical role in promoting growth and differentiation of intrathymic T cell precursors at early stages of T cell development.

scholarly journals Selective outgrowth of CD45RO+ V gamma 9+/V delta 2+ T-cell receptor gamma/delta T cells early after bone marrow transplantation

Blood ◽  
1991 ◽  
Vol 78 (7) ◽  
pp. 1875-1881 ◽  
Author(s):  
D van der Harst ◽  
A Brand ◽  
SA van Luxemburg-Heijs ◽  
YM Kooij-Winkelaar ◽  
FE Zwaan ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
T Cell ◽  
Mononuclear Cells ◽  
Cell Receptor ◽  
Gamma Delta T Cells ◽  
Gamma Delta ◽  
Delta Cells ◽  
Selective Outgrowth ◽  
Gamma Delta Cells

Before and after bone marrow transplantation (BMT) for hematologic malignancies, peripheral blood mononuclear cells from 10 patients were obtained. The relative and absolute numbers of CD3+ T-cell receptor gamma delta+ (TCR gamma delta+) cells, as defined by the reaction of monoclonal antibodies (MoAbs) directed against CD3 and the TCR gamma delta (anti-TCR gamma delta-1), were determined. Before transplantation, eight of nine patients tested had less than 10% CD3+TCR gamma delta+ cells. Consistent increased numbers of gamma delta cells up to eightfold the pretransplant level can be seen in four of nine patients tested within the first 4 months after BMT. The large majority of early posttransplant gamma delta and alpha beta T cells express the CD45RO antigen, which is usually expressed on “memory” cells only. The V-region usage of the TCR gamma delta+ T cells was analyzed using fresh mononuclear cells and MoAbs against known V gamma and V delta regions. For more detailed analysis, CD3+TCR gamma delta+ cells were sorted and cultured in bulk and cloned. Using fresh cells and bulk cultures, mainly V gamma 9+V delta 1-V delta 2+ cells were found during engraftment. Only after 6 weeks post-BMT, V gamma 9-V delta 1+V delta 2- cells appear. Analysis of the V gamma and V delta usage at the clonal level confirmed the observation that early after BMT only V gamma 9+V delta 2+ cells are present, whereas gamma delta T- cell clones expressing other gamma delta TCR phenotypes can only be detected 4 to 6 weeks post-BMT. The predominance of V gamma 9+ cells during early engraftment could be explained by several mechanisms: (A) sequential rearrangements during T-cell development, leading to an early wave of V gamma 9+ cells, or (B) selective outgrowth of preexisting V gamma 9+V delta 2+CD45RO+ TCR gamma delta cells in the bone marrow graft, possibly as a result of antigen driven expansion due to exposure to environmental antigens.

scholarly journals Selective outgrowth of CD45RO+ V gamma 9+/V delta 2+ T-cell receptor gamma/delta T cells early after bone marrow transplantation

Blood ◽  
1991 ◽  
Vol 78 (7) ◽  
pp. 1875-1881 ◽  
Author(s):  
D van der Harst ◽  
A Brand ◽  
SA van Luxemburg-Heijs ◽  
YM Kooij-Winkelaar ◽  
FE Zwaan ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
T Cell ◽  
Mononuclear Cells ◽  
Cell Receptor ◽  
Gamma Delta T Cells ◽  
Gamma Delta ◽  
Delta Cells ◽  
Selective Outgrowth ◽  
Gamma Delta Cells

Abstract Before and after bone marrow transplantation (BMT) for hematologic malignancies, peripheral blood mononuclear cells from 10 patients were obtained. The relative and absolute numbers of CD3+ T-cell receptor gamma delta+ (TCR gamma delta+) cells, as defined by the reaction of monoclonal antibodies (MoAbs) directed against CD3 and the TCR gamma delta (anti-TCR gamma delta-1), were determined. Before transplantation, eight of nine patients tested had less than 10% CD3+TCR gamma delta+ cells. Consistent increased numbers of gamma delta cells up to eightfold the pretransplant level can be seen in four of nine patients tested within the first 4 months after BMT. The large majority of early posttransplant gamma delta and alpha beta T cells express the CD45RO antigen, which is usually expressed on “memory” cells only. The V-region usage of the TCR gamma delta+ T cells was analyzed using fresh mononuclear cells and MoAbs against known V gamma and V delta regions. For more detailed analysis, CD3+TCR gamma delta+ cells were sorted and cultured in bulk and cloned. Using fresh cells and bulk cultures, mainly V gamma 9+V delta 1-V delta 2+ cells were found during engraftment. Only after 6 weeks post-BMT, V gamma 9-V delta 1+V delta 2- cells appear. Analysis of the V gamma and V delta usage at the clonal level confirmed the observation that early after BMT only V gamma 9+V delta 2+ cells are present, whereas gamma delta T- cell clones expressing other gamma delta TCR phenotypes can only be detected 4 to 6 weeks post-BMT. The predominance of V gamma 9+ cells during early engraftment could be explained by several mechanisms: (A) sequential rearrangements during T-cell development, leading to an early wave of V gamma 9+ cells, or (B) selective outgrowth of preexisting V gamma 9+V delta 2+CD45RO+ TCR gamma delta cells in the bone marrow graft, possibly as a result of antigen driven expansion due to exposure to environmental antigens.

scholarly journals Origin of human T-lymphotrophic virus I-positive T cell lines in adult T cell leukemia. Analysis of T cell receptor gene rearrangement.

1985 ◽  
Vol 162 (6) ◽  
pp. 2169-2174 ◽  
Author(s):  
M Maeda ◽  
A Shimizu ◽  
K Ikuta ◽  
H Okamoto ◽  
M Kashihara ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Lines ◽  
Receptor Gene ◽  
Cell Receptor ◽  
Leukemic Cells ◽  
T Cell Receptor Gene ◽  
T Cell Lines ◽  
Cell Receptor Gene

Using the clone-specific rearrangement of the T cell receptor gene as the genetic marker of the clonotype, we analyzed the clonal origin of the interleukin 2 (IL-2)-dependent human T-lymphotrophic virus I (HTLV-I)-positive T cell lines established from various adult T cell leukemia (ATL) patients. From a patient with chronic ATL, whose leukemic cells proliferated in vitro in response to IL-2, we repeatedly established leukemic T cell clones having the same rearrangement profile of the T beta chain gene as the leukemic cells. By contrast, established cell lines from acute ATL patients had different beta chain gene rearrangements from those of the leukemic cells. These HTLV-I+ T cell lines might not be the direct progeny of the leukemic cells, but that of T cells infected either in vivo or in vitro. These IL-2-reactive nonleukemic T cells might have been selected in vitro, because their leukemic cells failed to respond to IL-2, despite the expression of IL-2 receptor. The analysis of the T cell receptor gene rearrangement may give a new approach for the elucidation of the mechanism of leukemogenesis and the origin of the HTLV-I+ T cell lines in ATL.

scholarly journals Human T-lymphotropic virus I-infected T cells constitutively express lymphotoxin in vitro

Blood ◽  
1989 ◽  
Vol 73 (1) ◽  
pp. 194-201
Author(s):  
E Tschachler ◽  
M Robert-Guroff ◽  
RC Gallo ◽  
MS Jr Reitz
Keyword(s):  
T Cell ◽  
Cell Lines ◽  
Cell Clone ◽  
Biologically Active ◽  
Tnf Alpha ◽  
Type I ◽  
T Lymphotropic Virus ◽  
T Cell Clone ◽  
T Cell Lines

We have studied the pattern of expression of the lymphokines tumor necrosis factor (TNF alpha) and lymphotoxin (TNF beta) in T-cell lines established by transformation with human T-lymphotropic virus, type I (HTLV-I), the etiologic agent of adult T-cell leukemia (ATL). We report here that nine of nine HTLV-I-infected T-cell lines, established by in vitro infection with HTLV-I, including those with CD4+ or CD8+ as well as CD4-/CD8- phenotypes, constitutively produce high levels of TNF alpha and -beta mRNA and secrete biologically active TNF beta into the culture medium. Similar patterns of expression are seen in six of six HTLV-I-infected T-cell lines directly established from ATL patients. In contrast, several T-cell lines, either uninfected or infected with human immunodeficiency virus I, did not produce comparable levels of the TNF beta. Comparisons of a normal functional T-cell clone before and after infection with HTLV-I show that expression of TNF beta mRNA is induced in the infected cells. The high level expression in HTLV-I- infected cell lines dose not seem to involve perturbation of the TNF alpha/beta genetic loci by proviral integration. A cell line (81–66/45) nonproductively transformed with HTLV-I that produces tat-1 in the absence of viral structural proteins, produces both TNF alpha and -beta mRNA. This suggests that expression of these cytokines could be mediated in trans by the tat-1 gene product.

Transcription of germ line V alpha segments correlates with ongoing T-cell receptor alpha-chain rearrangement

1992 ◽  
Vol 12 (4) ◽  
pp. 1480-1489
Author(s):  
J D Fondell ◽  
K B Marcu
Keyword(s):  
T Cell ◽  
Cell Lines ◽  
Germ Line ◽  
Antigen Receptor ◽  
Cell Receptor ◽  
Alpha Chain ◽  
Recombination Activating Genes ◽  
Rag 1 ◽  
T Cell Lines

M14T is a virally transformed immature T-cell line which continues to rearrange its T-cell antigen receptor (TCR) alpha-chain genes in vitro and thus represents a dynamic system for studying TCR assembly. In an effort to investigate whether the TCR alpha locus is accessible for V(D)J rearrangement events, we examined M14T cells for the presence of germ line TCR alpha transcripts. Several unrearranged V alpha segments were found to be transcriptionally active in M14T cells. By comparison, germ line V alpha transcripts are absent in nonlymphoid and pro-T-cell lines and barely detectable in mature T-cell lines, suggesting that this phenomenon is likely stage and tissue specific. We demonstrate a perfect correlation between transcriptionally active V alpha segments and their involvement in ongoing V alpha-to-J alpha rearrangements. In addition, data suggesting that the unrearranged J alpha locus is also transcriptionally active in the M14T line are presented. Furthermore, the recombination-activating genes RAG-1 and RAG-2 are differentially expressed, with RAG-2 detectable only by polymerase chain reaction, implying that very low levels of one of these gene products are sufficient to complement the other to facilitate VJ rearrangements. These findings provide the first direct evidence for an accessibility model of antigen receptor rearrangement in T cells.

scholarly journals T cell receptor (TCR) beta chain homodimers on the surface of immature but not mature alpha, gamma, delta chain deficient T cell lines.

1992 ◽  
Vol 11 (7) ◽  
pp. 2735-2745 ◽  
Author(s):  
M. Groettrup ◽  
A. Baron ◽  
G. Griffiths ◽  
R. Palacios ◽  
H. von Boehmer
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Lines ◽  
Cell Receptor ◽  
Beta Chain ◽  
Gamma Delta ◽  
T Cell Lines

scholarly journals Human and Simian T-Cell Leukemia Viruses Type 2 (HTLV-2 and STLV-2pan-p) Transform T Cells Independently of Jak/STAT Activation

1998 ◽  
Vol 72 (5) ◽  
pp. 4408-4412 ◽  
Author(s):  
James C. Mulloy ◽  
Thi-Sau Migone ◽  
Ted M. Ross ◽  
Nick Ton ◽  
Patrick L. Green ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Lines ◽  
T Lymphotropic Virus ◽  
Stat Proteins ◽  
Constitutive Activation ◽  
T Cell Lines ◽  
Stat Pathway

ABSTRACT Human T-lymphotropic virus type 1 (HTLV-1) and HTLV-2 differ in pathogenicity in vivo. HTLV-1 causes leukemia and neurologic and inflammatory diseases, whereas HTLV-2 is less clearly associated with human disease. Both retroviruses transform human T cells in vitro, and transformation by HTLV-1 was found to be associated with the constitutive activation of the Jak/STAT pathway. To assess whether HTLV-2 transformation may also result in constitutive activation of the Jak/STAT pathway, six interleukin-2-independent, HTLV-2-transformed T-cell lines were analyzed for the presence of activated Jak and STAT proteins by electrophoretic mobility shift assay. In addition, the phosphorylation status of Jak and STAT proteins was assessed directly by immunoprecipitation and immunoblotting with an antiphosphotyrosine antibody. Jak/STAT proteins were not found to be constitutively activated in any of the T-cell lines infected by the type 2 human and nonhuman primate viruses, suggesting that HTLV-2 and the cognate virus simian T-lymphotropic virus type 2 from Pan paniscustransform T cells in vitro by mechanisms at least partially different from those used by HTLV-1.

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