In vitro negative selection of αβ T cell receptor transgenic thymocytes by conditionally immortalized thymic cortical epithelial cell lines and dendritic cells

T-cell negative selection, a process by which intrathymic immunological tolerance is induced, involves the apoptosis-mediated clonal deletion of potentially autoreactive T cells. Although different experimental approaches suggest that this process is triggered as the result of activation-mediated cell death, the signal transduction pathways underlying this process is not fully understood. In the present report we have used an in vitro system to analyze the cell activation and proliferation requirements for the deletion of viral superantigen (SAg)-reactive Vβ8.1 T-cell receptor (TCR) transgenic (TG) thymocytes. Our results indicate that in vitro negative selection of viral SAg-reactive CD4+ CD8+thymocytes is dependent on thymocyte activation but does not require the proliferation of the negatively signaled thymocytes.

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FK506 inhibits the differentiation of developing thymocytes but not negative selection of T cell receptor Vβ5+ and Vβ;11+ T lymphocytes in vivo

Transplant Immunology ◽

10.1016/0966-3274(94)90072-8 ◽

1994 ◽

Vol 2 (1) ◽

pp. 11-21 ◽

Cited By ~ 6

Author(s):

Jacky Woo ◽

Suzanne T. Ildstad ◽

Angus W. Thomson

Keyword(s):

T Cell ◽

T Lymphocytes ◽

T Cell Receptor ◽

Negative Selection ◽

Cell Receptor ◽

Selection Of

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Selection of Distinct Valpha/beta T-Cell Receptor Families During In Vivo and In Vitro T-Cell Maturation

Scandinavian Journal of Immunology ◽

10.1046/j.1365-3083.1999.00527.x ◽

1999 ◽

Vol 49 (5) ◽

pp. 474-480

Author(s):

Caccamo ◽

Sireci ◽

Ivanyi ◽

Salerno ◽

Dieli

Keyword(s):

T Cell ◽

T Cell Receptor ◽

Cell Receptor ◽

Cell Maturation ◽

T Cell Maturation ◽

Selection Of

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

Journal of Experimental Medicine ◽

10.1084/jem.162.6.2169 ◽

1985 ◽

Vol 162 (6) ◽

pp. 2169-2174 ◽

Cited By ~ 118

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.

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Viral Superantigen-Induced Negative Selection of TCR Transgenic CD4+ CD8+ Thymocytes Depends on Activation, but not Proliferation

Blood ◽

10.1182/blood.v91.11.4248 ◽

1998 ◽

Vol 91 (11) ◽

pp. 4248-4254 ◽

Cited By ~ 2

Author(s):

Isabel Ferrero ◽

Fabienne Anjuère ◽

Iñigo Azcoitia ◽

Toufic Renno ◽

H. Robson MacDonald ◽

...

Keyword(s):

T Cell ◽

Negative Selection ◽

Cell Activation ◽

Present Report ◽

Cell Receptor ◽

Immunological Tolerance ◽

Clonal Deletion ◽

Experimental Approaches ◽

Selection Of

Abstract T-cell negative selection, a process by which intrathymic immunological tolerance is induced, involves the apoptosis-mediated clonal deletion of potentially autoreactive T cells. Although different experimental approaches suggest that this process is triggered as the result of activation-mediated cell death, the signal transduction pathways underlying this process is not fully understood. In the present report we have used an in vitro system to analyze the cell activation and proliferation requirements for the deletion of viral superantigen (SAg)-reactive Vβ8.1 T-cell receptor (TCR) transgenic (TG) thymocytes. Our results indicate that in vitro negative selection of viral SAg-reactive CD4+ CD8+thymocytes is dependent on thymocyte activation but does not require the proliferation of the negatively signaled thymocytes.

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T cell receptor-mediated negative selection of autoreactive T lymphocyte precursors occurs after commitment to the CD4 or CD8 lineages.

Journal of Experimental Medicine ◽

10.1084/jem.172.3.835 ◽

1990 ◽

Vol 172 (3) ◽

pp. 835-845 ◽

Cited By ~ 120

Author(s):

C J Guidos ◽

J S Danska ◽

C G Fathman ◽

I L Weissman

Keyword(s):

Major Histocompatibility Complex ◽

T Cell ◽

T Cell Receptor ◽

T Lymphocyte ◽

Negative Selection ◽

Cell Receptor ◽

Histocompatibility Complex ◽

Show Evidence ◽

Maturational Stage ◽

Selection Of

To identify the maturational stage(s) during which T cell receptor (TCR)-mediated positive and negative selection occurs, we followed the development of CD4+8- and CD4-8+ T cells from TCRlo CD4+8+ thymic blasts in the presence of different positive and negative selecting (major histocompatibility complex or Mls) elements. We describe novel lineage-committed transitional intermediates that are TCRmed CD4+8lo or TCRmed CD4lo8+, and that show evidence of having been positively selected. Furthermore, negative selection is not evident until after cells have attained one of the TCRmed transitional phenotypes. Accordingly, we propose that negative selection in normal mice occurs only after TCRlo CD4+8+ precursors have been positively selected into either the CD4 or CD8 lineage.

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Thymus-independent development and negative selection of T cells expressing T cell receptor alpha/beta in the intestinal epithelium: evidence for distinct circulation patterns of gut- and thymus-derived T lymphocytes.

Journal of Experimental Medicine ◽

10.1084/jem.176.1.187 ◽

1992 ◽

Vol 176 (1) ◽

pp. 187-199 ◽

Cited By ~ 187

Author(s):

P Poussier ◽

P Edouard ◽

C Lee ◽

M Binnie ◽

M Julius

Keyword(s):

T Cells ◽

T Cell ◽

Lamina Propria ◽

T Cell Receptor ◽

Intestinal Epithelium ◽

Negative Selection ◽

Cell Receptor ◽

Normal Numbers ◽

Alpha Beta ◽

Selection Of

We demonstrate that mouse intestinal intraepithelial lymphocytes (IEL) can be divided into subsets based on the differential expression of functional T cell receptor alpha/beta (TCR-alpha/beta) signaling complexes. Two subsets, CD4+ 8 alpha + beta - and CD8 alpha + beta -, are refractory to stimulation with anti-TCR-alpha/beta and contain high frequencies of potentially self-reactive cells. In contrast, the CD4+ and CD8 alpha + beta + IEL subsets are responsive to anti-TCR-alpha/beta and depleted of potentially self-reactive cells. The analysis of fetal liver radiation chimeras using adult thymectomized recipients demonstrates that the four TCR-alpha/beta + IEL subsets are generated in normal numbers in the absence of the thymus. Moreover, expression of the major histocompatibility complex class II-encoded I-E molecule and Mls1a in the gut of the athymic host results in the negative selection of potentially self-reactive T cells expressing V beta 11 and V beta 6, respectively, from those IEL subsets that express functional TCR-alpha/beta signaling complexes. Neither the spleen nor the Peyer's patches of athymic recipients contain T cells of donor origin. In contrast, normal numbers of phenotypically and functionally mature CD4+ and CD8 alpha + beta + T cells of donor origin are found in the lamina propria of chimeric animals. The phenotypic analysis of lymphocytes obtained from Ly5 congenic parabionts reveals that peripheral T cells migrate rapidly to the Peyer's patches and lamina propria, but not to the intestinal epithelium. Taken together, these results demonstrate that the intestinal epithelium is a thymus-independent site of T lymphopoiesis, where selection of the T cell repertoire involves the deletion of potentially self-reactive cells in situ. Moreover, the appearance of donor-derived, phenotypically mature T cells, exclusively in the lamina propria of athymic radiation chimeras, suggests that mature IEL expressing functional TCR-alpha/beta migrate to this site.

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