scholarly journals Expression and rearrangement of the alpha, beta, and gamma chain genes of the T cell receptor in cloned murine large granular lymphocyte lines. No correlation with the cytotoxic spectrum.

1986 ◽  
Vol 164 (2) ◽  
pp. 428-442 ◽  
Author(s):  
K Ikuta ◽  
M Hattori ◽  
K Wake ◽  
S Kano ◽  
T Honjo ◽  
...  
Keyword(s):  
T Cell ◽  
Nk Cells ◽  
T Cell Receptor ◽  
Blot Hybridization ◽  
Cell Receptor ◽  
Chain Gene ◽  
Northern Blot Hybridization ◽  
Beta Chain ◽  
Gamma Chain ◽  
Alpha Beta

Using cloned murine large granular lymphocyte (LGL) lines, the expression and the rearrangement of the alpha, beta, and gamma chain genes of the T cell receptor (TCR) were analyzed. Morphological, phenotypical, as well as functional studies indicated that the LGL lines were identical to normal, endogenous NK cells. Northern blot hybridization analysis indicated that the full-length transcripts of all the alpha, beta, and gamma chain genes were expressed in most of the LGL lines, including two lines derived from athymic nude mice. In one line, SPB, however, no transcript of the gamma chain gene was detected, whereas the alpha and beta chain genes were clearly expressed. In every LGL line studied, all of the alpha, beta, and gamma chain genes were rearranged. Conforming to the results of Northern blot hybridization study, the gamma chain gene of the SPB line was aberrantly rearranged, whereas those of all the other lines were productively rearranged. The results clearly revealed that NK cells represented a population of lymphocytes genetically committed to the T cell lineage. It was also suggested that the expression and rearrangement of the TCR genes of NK cells might occur in a thymus-independent fashion. An SPB line without expression of the gamma chain gene could exhibit NK activity indistinguishable from other NK lines. Furthermore, the rearrangement patterns of the beta chain gene did not correlate with the specificity of the cytotoxic activity. These results strongly suggested that the cytotoxic activity in NK cells was not directly mediated by TCR on them. We particularly noted that the beta chain gene of most independently established LGL lines showed identical patterns of rearrangement, indicating that they used the same V beta and J beta gene segments. The significance of the restricted pattern of rearrangement of the beta chain gene in LGL lines, as well as the possible functional roles of TCR on NK cells, was discussed.

scholarly journals Terminal deoxynucleotidyl transferase expression can precede T cell receptor beta chain and gamma chain rearrangement in T cell acute lymphoblastic leukemia

Blood ◽  
1987 ◽  
Vol 69 (1) ◽  
pp. 356-360
Author(s):  
JM Greenberg ◽  
JH Kersey
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
T Cell Receptor ◽  
Lymphoblastic Leukemia ◽  
Cell Receptor ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Beta Chain ◽  
Gamma Chain ◽  
T Cell Receptor Beta ◽  
Receptor Beta

The nuclear enzyme terminal deoxynucleotidyl transferase (TdT) is thought to contribute to the diversity of certain immunoglobulin and T cell receptor gene rearrangements through the addition of random nucleotides at their variable (V)-joining (J) region junctions. An acute lymphoblastic leukemia (ALL) with an immature T cell phenotype (CD7+, CD5+, CD1+/-, CD2+/-, CD3-, CD4-, CD8-) was found to be TdT+ with germline immunoglobulin heavy chain, T cell receptor beta chain, and T cell gamma chain genes. The data indicate that TdT expression can precede T gamma and T beta rearrangement during T lymphoid ontogeny consistent with its proposed association with the T cell receptor rearrangement process. Southern analysis of certain cases of T-ALL may not result in the detection of a monoclonal population of cells.

scholarly journals Activation via the CD3 and CD16 pathway mediates interleukin-2- dependent autocrine proliferation of granular lymphocytes in patients with granular lymphocyte proliferative disorders

Blood ◽  
1991 ◽  
Vol 78 (12) ◽  
pp. 3232-3240 ◽  
Author(s):  
S Hoshino ◽  
K Oshimi ◽  
M Teramura ◽  
H Mizoguchi
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Nk Cell ◽  
Interleukin 2 ◽  
Cell Lineage ◽  
Cell Receptor ◽  
Cell Phenotype ◽  
Beta Chain ◽  
Alpha Beta ◽  
Granular Lymphocytes

Abstract Granular lymphocytes (GLs) in patients with GL-proliferative disorders (GLPDs) are known to express the interleukin-2 receptor (IL-2R) beta chain (p70–75) constitutively and to proliferate in response to stimulation with IL-2 via the beta chain. In this report, we found that the anti-CD3 monoclonal antibody (MoAb) OKT3 could induce the proliferation of GLs from patients with T-cell lineage GLPDs (T-cell receptor-alpha beta+/CD3+16+), but not that of natural killer (NK) cell lineage GLs (T-cell receptor-alpha beta-/CD3–16+). In contrast, the anti-CD16 MoAb 3G8 that reacts with NK-lineage GLs could induce the proliferation of these GLs but not that of GLs with a T-cell phenotype. Furthermore, the anti-CD16 MoAbs CLB FcR gran1 (VD2) and OK-NK, which react with both T- and NK-lineage GLs, induced the proliferation of GLs with both T- and and NK-cell phenotypes. The proliferative response induced via the CD3 or IgG Fc receptor III (Fc gamma RIII: CD16) pathway was shown to be associated with the IL-2-dependent autocrine pathway by various findings, including the induction of endogenous IL-2 production, the coexpression of the IL-2R alpha chain (p55) and the IL- 2R beta chain, and the inhibition of GL proliferation by anti-IL-2 or anti-IL-2R MoAb. These results suggest that GL proliferation is mediated at least partly through the IL-2-dependent autocrine pathway, and that the TCR/CD3 complex in T-cell phenotype GLs and the Fc gamma RIII in both T- and NK-cell phenotype GLs play a role in their activation in GLPDs.

scholarly journals p70 lupus autoantigen binds the enhancer of the T-cell receptor beta-chain gene.

1993 ◽  
Vol 90 (7) ◽  
pp. 2685-2689 ◽  
Author(s):  
H. Messier ◽  
T. Fuller ◽  
S. Mangal ◽  
H. Brickner ◽  
S. Igarashi ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Chain Gene ◽  
Beta Chain ◽  
T Cell Receptor Beta ◽  
Receptor Beta

scholarly journals T-cell receptor beta-chain gene rearrangement and expression during human thymic ontogenesis

Blood ◽  
1992 ◽  
Vol 79 (6) ◽  
pp. 1472-1483 ◽  
Author(s):  
A Bonati ◽  
P Zanelli ◽  
S Ferrari ◽  
A Plebani ◽  
B Starcich ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Chain Gene ◽  
Gene Transcript ◽  
Beta Chain ◽  
Early Stages ◽  
Human Thymus ◽  
Nucleotide Insertions ◽  
Beta Gene

Abstract T-cell receptor (TCR) beta-chain proteins appear early (approximately 15th week of gestation) during human thymic ontogenesis. These beta- chain proteins, which appear before terminal deoxynucleotidyl transferase (TdT), could be an expression of a fully rearranged (V-D- J), incompletely rearranged (D-J), or germline TCR beta-chain gene. The aims of this study, performed from the 15th week onward, were the following: (1) to investigate whether or not TCR beta gene rearranges at an early stage during human thymic ontogenesis; (2) to investigate whether complete presumptive functional (1.3 kb) TCR beta gene transcript is present at these early stages of development, or if incomplete (1 kb) or germ-line (1.1 kb) transcripts are expressed; (3) to examine the phenotype of TCR beta-chain+ cells with two-color fluorescence using monoclonal antibody (MoAb) beta F1 and MoAbs that recognize CD1, CD2, CD3, CD4, CD8, CD5, and CD7 antigens (rabbit anti- calf TdT antiserum was used to detect TdT); and (4) to demonstrate whether or not beta gene N-diversity regions are detectable as early as the 15th week and whether or not N-nucleotide insertions correlate to TdT expression. Fifteen- to 22-week fetal thymuses and pediatric thymuses were investigated. We demonstrated that TCR beta-chain gene rearranged as early as the 15th week in human thymus and that a complete functional TCR beta gene transcript was expressed at these early stages of human development. No other analyses to date have investigated TCR beta gene expression in early human thymus using molecular biology techniques. No significant differences were detectable between phenotypic analysis of fetal and pediatric samples, except for TdT expression, which appeared after the 20th week. Essentially all mCD3+ (OKT3+) cells were beta-chain+ at the different weeks investigated. A significant percentage of CD1+ cells were beta- chain+, and the percentage increased along with the age of development. After the 20th week, we identified three main populations: TdT+, cCD3+, beta F-(early thymic precursors); TdT+, CD1+, beta F1+ (intermediate maturity cortical thymocytes); and TdT-, mCD3+, beta F1++ (mature medullary thymocytes). Given these values, we may consider beta-chain expression an ordered process. beta gene N-nucleotide insertions were correlated to TdT expression, since N-regions increased considerably after the 20th week. A further increase of N-nucleotide insertions was detected from the 22nd week to the 32nd week.

scholarly journals Terminal deoxynucleotidyl transferase expression can precede T cell receptor beta chain and gamma chain rearrangement in T cell acute lymphoblastic leukemia

Blood ◽  
1987 ◽  
Vol 69 (1) ◽  
pp. 356-360 ◽  
Author(s):  
JM Greenberg ◽  
JH Kersey
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
T Cell Receptor ◽  
Lymphoblastic Leukemia ◽  
Cell Receptor ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Beta Chain ◽  
Gamma Chain ◽  
T Cell Receptor Beta ◽  
Receptor Beta

Abstract The nuclear enzyme terminal deoxynucleotidyl transferase (TdT) is thought to contribute to the diversity of certain immunoglobulin and T cell receptor gene rearrangements through the addition of random nucleotides at their variable (V)-joining (J) region junctions. An acute lymphoblastic leukemia (ALL) with an immature T cell phenotype (CD7+, CD5+, CD1+/-, CD2+/-, CD3-, CD4-, CD8-) was found to be TdT+ with germline immunoglobulin heavy chain, T cell receptor beta chain, and T cell gamma chain genes. The data indicate that TdT expression can precede T gamma and T beta rearrangement during T lymphoid ontogeny consistent with its proposed association with the T cell receptor rearrangement process. Southern analysis of certain cases of T-ALL may not result in the detection of a monoclonal population of cells.

scholarly journals Fc gamma RII/III and CD2 expression mark distinct subpopulations of immature CD4-CD8- murine thymocytes: in vivo developmental kinetics and T cell receptor beta chain rearrangement status.

1993 ◽  
Vol 177 (4) ◽  
pp. 1079-1092 ◽  
Author(s):  
H R Rodewald ◽  
K Awad ◽  
P Moingeon ◽  
L D'Adamio ◽  
D Rabinowitz ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Fetal Development ◽  
Cell Receptor ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Immunoglobulin Gene ◽  
Beta Chain ◽  
Double Positive ◽  
Alpha Beta

We have recently identified a dominant wave of CD4-CD8- (double-negative [DN]) thymocytes in early murine fetal development that express low affinity Fc gamma receptors (Fc gamma RII/III) and contain precursors for Ti alpha/beta lineage T cells. Here we show that Fc gamma RII/III is expressed in very immature CD4low single-positive (SP) thymocytes and that Fc gamma RII/III expression is downregulated within the DN subpopulation and before the CD3-CD8low SP stage in T cell receptor (TCR)-alpha/beta lineage-committed thymocytes. DN Fc gamma RII/III+ thymocytes also contain a small fraction of TCR-gamma/delta lineage cells in addition to TCR-alpha/beta progenitors. Fetal day 15.5 DN TCR-alpha/beta lineage progenitors can be subdivided into three major subpopulations as characterized by cell surface expression of Fc gamma RII/III vs. CD2 (Fc gamma RII/III+CD2-, Fc gamma RII/III+CD2+, Fc gamma RII/III-CD2+). Phenotypic analysis during fetal development as well as adoptive transfer of isolated fetal thymocyte subpopulations derived from C57B1/6 (Ly5.1) mice into normal, nonirradiated Ly5.2 congenic recipient mice identifies one early differentiation sequence (Fc gamma RII/III+CD2(-)-->Fc gamma RII/III+CD2(+)-->Fc gamma RII/III-CD2+) that precedes the entry of DN thymocytes into the CD4+CD8+ double-positive (DP) TCRlow/- stage. Unseparated day 15.5 fetal thymocytes develop into DP thymocytes within 2.5 d and remain at the DP stage for > 48 h before being selected into either CD4+ or CD8+ SP thymocytes. In contrast, Fc gamma RII/III+CD2- DN thymocytes follow this same developmental pathway but are delayed by approximately 24 h before entering the DP compartment, while Fc gamma RII/III-CD2+ display accelerated development by approximately 24 h compared with total day 15.5 thymocytes. Fc gamma RII/III-CD2+ are also more developmentally advanced than Fc gamma RII/III+CD2- fetal thymocytes with respect to their TCR beta chain V(D)J rearrangement. At day 15.5 in gestation, beta chain V(D)J rearrangement is mostly, if not entirely, restricted to the Fc gamma RII/III-CD2+ subset of DN fetal thymocytes. Consistent with this analysis in fetal thymocytes, > 90% of adult thymocytes derived from mice carrying a disrupting mutation at the recombination-activating gene 2 locus (RAG-2-/-) on both alleles are developmentally arrested at the DN CD2- stage. In addition, there is a fivefold increase in the relative percentage of thymocytes expressing Fc gamma RII/III in TCR and immunoglobulin gene rearrangement-incompetent homozygous RAG-2-/- mice (15% Fc gamma RII/III+) versus rearrangement-competent heterozygous RAG-2+/- mice (< 3% Fc gamma RII/III+). Thus, Fc gamma RII/III expression defines an early DN stage preceding V beta(D beta)I beta rearrangement, which in turn is followed by surface expression of CD2. Loss of Fc gamma RII/III and acquisition of CD2 expression characterize a late DN stage immediately before the conversion into DP thymocytes.

scholarly journals Regulation of pre-T cell receptor (pT alpha-TCR beta) gene expression during human thymic development.

1996 ◽  
Vol 184 (2) ◽  
pp. 519-530 ◽  
Author(s):  
A R Ramiro ◽  
C Trigueros ◽  
C Márquez ◽  
J L San Millán ◽  
M L Toribio
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
T Cell Development ◽  
Cell Receptor ◽  
Beta Chain ◽  
Thymocyte Development ◽  
Gene Encoding ◽  
Thymic Development ◽  
Alpha Beta ◽  
Beta Gene

In murine T cell development, early thymocytes that productively rearrange the T cell receptor (TCR) beta locus are selected to continue maturation, before TCR alpha expression, by means of a pre-TCR alpha- (pT alpha-) TCR beta heterodimer (pre-TCR). The aim of this study was to identify equivalent stages in human thymocyte development. We show here that variable-diversity-joining region TCR beta rearrangement and the expression of full-length TCR beta transcripts have been initiated in some immature thymocytes at the TCR alpha/beta- CD4+CD8- stage, and become common in a downstream subset of TCR alpha/beta- CD4+CD8+ thymocytes that is highly enriched in large cycling cells. TCR beta chain expression was hardly detected in TCR alpha/beta- CD4+CD8- thymocytes, whereas cytoplasmic TCR beta chain was found in virtually all TCR alpha/beta- CD4+CD8+ blasts. In addition, a TCR beta complex distinct from the mature TCR alpha/beta heterodimer was immunoprecipitated only from the latter subset. cDNA derived from TCR alpha/beta- CD4+CD8+ blasts allowed us to identify and clone the gene encoding the human pT alpha chain, and to examine its expression at different stages of thymocyte development. Our results show that high pT alpha transcription occurs only in CD4+CD8- and CD4+CD8+ TCR alpha/beta- thymocytes, whereas it is weaker in earlier and later stages of development. Based on these results, we propose that the transition from TCR alpha/beta- CD4+CD8- to TCR alpha/beta- CD4+CD8+ thymocytes represents a critical developmental stage at which the successful expression of TCR beta promotes the clonal expansion and further maturation of human thymocytes, independent of TCR alpha.

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