scholarly journals Premature Expression of T Cell Receptor (Tcr)αβ Suppresses Tcrγδ Gene Rearrangement but Permits Development of γδ Lineage T Cells

2000 ◽  
Vol 192 (4) ◽  
pp. 537-548 ◽  
Author(s):  
Kathleen Terrence ◽  
Christian P. Pavlovich ◽  
Errin O. Matechak ◽  
B.J. Fowlkes
Keyword(s):  
T Cells ◽  
T Cell ◽  
Transgenic Mice ◽  
T Cell Receptor ◽  
Cd8 T Cells ◽  
Gene Rearrangement ◽  
T Cell Development ◽  
Cell Receptor ◽  
Lineage Commitment ◽  
Cd8 Cells

The T cell receptor (TCR)γδ and the pre-TCR promote survival and maturation of early thymocyte precursors. Whether these receptors also influence γδ versus αβ lineage determination is less clear. We show here that TCRγδ gene rearrangements are suppressed in TCRαβ transgenic mice when the TCRαβ is expressed early in T cell development. This situation offers the opportunity to examine the outcome of γδ versus αβ T lineage commitment when only the TCRαβ is expressed. We find that precursor thymocytes expressing TCRαβ not only mature in the αβ pathway as expected, but also as CD4−CD8− T cells with properties of γδ lineage cells. In TCRαβ transgenic mice, in which the transgenic receptor is expressed relatively late, TCRγδ rearrangements occur normally such that TCRαβ+CD4−CD8− cells co-express TCRγδ. The results support the notion that TCRαβ can substitute for TCRγδ to permit a γδ lineage choice and maturation in the γδ lineage. The findings could fit a model in which lineage commitment is determined before or independent of TCR gene rearrangement. However, these results could be compatible with a model in which distinct signals bias lineage choice and these signaling differences are not absolute or intrinsic to the specific TCR structure.

scholarly journals Expression of two alpha chains on the surface of T cells in T cell receptor transgenic mice.

1993 ◽  
Vol 178 (5) ◽  
pp. 1807-1811 ◽  
Author(s):  
W R Heath ◽  
J F Miller
Keyword(s):  
T Cells ◽  
T Cell ◽  
Transgenic Mice ◽  
T Cell Receptor ◽  
Cd8 T Cells ◽  
Flow Cytometric Analysis ◽  
Cell Receptor ◽  
Specific Monoclonal Antibody ◽  
Beta Chain ◽  
Flow Cytometric

CD8+ T cells taken directly from mice expressing a Kb-specific T cell receptor (TCR) transgene expressed the transgenic TCR in a bimodal profile as detected by flow cytometric analysis using a clonotype-specific monoclonal antibody. Those cells expressing the lower density of the transgenic TCR expressed the transgenic beta chain and two different alpha chains on their surface. One alpha chain was the product of the alpha transgene, whereas the other was derived by endogenous rearrangement. This report provides the first demonstration that T cells isolated directly from mice may express two different TCR clonotypes on their surface. The potential consequences of this finding for studies using TCR transgenic mice and for the induction of autoimmunity are discussed.

scholarly journals Evidence That γδ versus αβ T Cell Fate Determination Is Initiated Independently of T Cell Receptor Signaling

2001 ◽  
Vol 193 (6) ◽  
pp. 689-698 ◽  
Author(s):  
Joonsoo Kang ◽  
Ariane Volkmann ◽  
David H. Raulet
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Fate ◽  
T Cell Receptor ◽  
Gene Rearrangement ◽  
Γδ T Cells ◽  
Cell Receptor ◽  
Developmental Potential ◽  
Cd8 Cells ◽  
Interleukin 7

Two types of T cells, αβ and γδ, develop in vertebrates. How these two T cell lineages arise from a common thymic T progenitor is poorly understood. Differentiation of αβ lineage T cells requires the surrogate α chain (pTα), which associates with the T cell receptor (TCR) β chain to form the pre-TCR. γδ lineage development does not appear to involve an obligatory surrogate chain, but instead requires productive rearrangement and expression of both TCR γ and δ genes. It has been proposed that the quality of signals transmitted by the pre-TCR and γδ TCR are distinct and that these “instructive” signals determine the lineage fate of an uncommitted progenitor cell. Here we show that the thymic T progenitor cells (CD25+CD44+c-kit+CD3−CD4−CD8− thymocytes, termed pro-T cells) from young adult mice that have yet to express TCRs can be subdivided based on interleukin 7 receptor (IL-7R) expression. These subsets exhibit differential potential to develop into γδ versus αβ lineage (CD4+CD8+ cells) in the thymus. Upon intrathymic injection, IL-7Rneg-lo pro-T cells generated a 13-fold higher ratio of αβ lineage to γδ lineage cells than did IL-7R+ pro-T cells. Much of this difference was due to a fivefold greater potential of IL-7R+ pro-T cells to develop into TCR-γδ T cells. Evidence indicates that this biased developmental potential is not a result of enhanced TCR-γ gene rearrangement/expression in IL-7R+ pro-T cells. These results indicate that the pro-T cells are heterogeneous in developmental potential before TCR gene rearrangement and suggest that in some precursor cells the initial lineage commitment is independent of TCR-mediated signals.

Self-reactive memory-phenotype CD8 T cells exhibit both MHC-restricted and non-MHC-restricted cytotoxicity: a role for the T-cell receptor and natural killer cell receptors

Blood ◽  
2004 ◽  
Vol 104 (7) ◽  
pp. 2116-2123 ◽  
Author(s):  
Salim Dhanji ◽  
Soo-Jeet Teh ◽  
Darryl Oble ◽  
John J. Priatel ◽  
Hung-Sia Teh
Keyword(s):  
T Cells ◽  
T Cell ◽  
Transgenic Mice ◽  
Natural Killer ◽  
T Cell Receptor ◽  
Cd8 T Cells ◽  
Adaptor Protein ◽  
Cell Receptor ◽  
Target Cells ◽  
Lymphoid Tissues

Abstract We have recently shown that interleukin-2 (IL-2)-activated CD8+CD44hi cells from normal mice express both adaptive and innate immune system receptors and specifically kill syngeneic tumor cells, particularly those that express NKG2D ligands. Here we show that CD8+ T cells from antigen-expressing H-Y T-cell receptor (TCR) transgenic mice also exhibit characteristics of both T cells and natural killer (NK) cells. Interaction with cognate self-antigen was required for the optimal expansion of these cells in peripheral lymphoid tissues. Although these cells possess a higher activation threshold relative to naive T cells, they can be activated by cytokine alone in vitro. They also undergo bystander proliferation in response to a bacterial infection in vivo. Interestingly, upon activation, the cells express the NKG2D receptor as well as the DNAX activation protein 12 (DAP12) adaptor protein. We provide evidence that NKG2D can act additively with the TCR in the killing of target cells, and it can also function as a directly activating receptor in non-major histocompatibility complex (MHC)-restricted killing of target cells. These properties of CD8+ T cells from H-Y TCR transgenic mice are remarkably similar to CD8+CD44hi cells that are found in normal mice. The H-Y TCR transgenic mice provide a well-defined system for characterizing the developmental biology and function of these cells. (Blood. 2004;104:2116-2123)

scholarly journals Both intrathymic and peripheral selection modulate the differential expression of V beta 5 among CD4+ and CD8+ T cells.

1992 ◽  
Vol 176 (6) ◽  
pp. 1733-1738 ◽  
Author(s):  
P J Fink ◽  
K Swan ◽  
G Turk ◽  
M W Moore ◽  
F R Carbone
Keyword(s):  
T Cells ◽  
T Cell ◽  
Transgenic Mice ◽  
Cd8 T Cells ◽  
Cell Receptor ◽  
T Cell Subsets ◽  
Gene Encoding ◽  
Cd8 Cells ◽  
Peripheral T Cells

Murine T cells expressing V beta 5 are characterized by (a) intrathymic deletion in the presence of I-E and products of endogenous mouse mammary tumor viruses, and (b) a greater representation in CD8+ relative to CD4+ peripheral T cells, thought to be due to more efficient intrathymic positive selection on class I rather than class II major histocompatibility complex antigens. We have engineered mice that are transgenic for a rearranged gene encoding a V beta 5+ beta chain of the T cell receptor for antigen. Deletion is not predicted in I-E- V beta 5+ transgenic mice, and until the age of 2 wk, the CD4/CD8 ratio of peripheral T cells is > 3:1 and indistinguishable between transgenic and nontransgenic mice. Transgenic mice then show a rapid, age-dependent decline in the ratio of CD4+ to CD8+ T cells in the lymphoid periphery, reaching a low of 1:10 by 7 mo of age. Furthermore, the percent of peripheral CD4+ cells that express the transgene drops with age, reaching a low of about 60% at 7 mo, while the percent of CD8+ cells that express V beta 5 remains greater than 95% at all ages. The lymphoid periphery is implicated in this selection against CD4+ V beta 5+ T cells as it occurs more rapidly in thymectomized transgenic mice, and can be delayed in mice whose peripheral T cells are replaced by recent thymic emigrants after depletion by in vivo treatment with anti-Thy-1 antibodies. These results indicate that the relative expression of V beta 5 in T cell subsets can be influenced not only intrathymically in I-E+ V beta 5+ transgenic mice, but also by events in the periphery, in the absence of I-E expression.

scholarly journals CD4+ T Cells from Glutamic Acid Decarboxylase (GAD)65-specific T Cell Receptor Transgenic Mice Are Not Diabetogenic and Can Delay Diabetes Transfer

2002 ◽  
Vol 196 (4) ◽  
pp. 481-492 ◽  
Author(s):  
Kristin V. Tarbell ◽  
Mark Lee ◽  
Erik Ranheim ◽  
Cheng Chi Chao ◽  
Maija Sanna ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Transgenic Mice ◽  
T Cell Receptor ◽  
Glutamic Acid Decarboxylase ◽  
Cd4 T Cells ◽  
Cell Receptor ◽  
Acid Decarboxylase ◽  
Gad 65

Glutamic acid decarboxylase (GAD)65 is an early and important antigen in both human diabetes mellitus and the nonobese diabetic (NOD) mouse. However, the exact role of GAD65-specific T cells in diabetes pathogenesis is unclear. T cell responses to GAD65 occur early in diabetes pathogenesis, yet only one GAD65-specific T cell clone of many identified can transfer diabetes. We have generated transgenic mice on the NOD background expressing a T cell receptor (TCR)-specific for peptide epitope 286–300 (p286) of GAD65. These mice have GAD65-specific CD4+ T cells, as shown by staining with an I-Ag7(p286) tetramer reagent. Lymphocytes from these TCR transgenic mice proliferate and make interferon γ, interleukin (IL)-2, tumor necrosis factor (TNF)-α, and IL-10 when stimulated in vitro with GAD65 peptide 286–300, yet these TCR transgenic animals do not spontaneously develop diabetes, and insulitis is virtually undetectable. Furthermore, in vitro activated CD4 T cells from GAD 286 TCR transgenic mice express higher levels of CTL-associated antigen (CTLA)-4 than nontransgenic littermates. CD4+ T cells, or p286-tetramer+CD4+ Tcells, from GAD65 286–300-specific TCR transgenic mice delay diabetes induced in NOD.scid mice by diabetic NOD spleen cells. This data suggests that GAD65 peptide 286–300-specific T cells have disease protective capacity and are not pathogenic.

scholarly journals Control of HIV-1 immune escape by CD8 T cells expressing enhanced T-cell receptor

2008 ◽  
Vol 14 (12) ◽  
pp. 1390-1395 ◽  
Author(s):  
Angel Varela-Rohena ◽  
Peter E Molloy ◽  
Steven M Dunn ◽  
Yi Li ◽  
Megan M Suhoski ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Cd8 T Cells ◽  
Immune Escape ◽  
Cell Receptor ◽  
Hiv 1
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