Abnormal T cell development in CD3-zeta-/- mutant mice and identification of a novel T cell population in the intestine.

Liu, C.P.; Ueda, R.; She, Jian; Sancho, Jaime; Wang, B.; Weddell, Gregory N.; Loring, Jeanne F.; Kurahara, Carole; Dudley, Erastus C.; Hayday, Adrian

doi:10.1002/j.1460-2075.1993.tb06176.x

Cited by 176 publications

(127 citation statements)

References 75 publications

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“…It is known that the´chain plays a critical role during thymocyte development [6,36,37]. Although the immunoreceptor tyrosine-based activation motif (ITAM) of thé chain may not be absolutely required for the development of T cells, the number of ITAM correlates with the efficiency of thymocyte selection in vivo [38].…”

Section: Discussionmentioning

confidence: 99%

“…The DOTCR + T cells are selected by the MHC class II I-A d molecules and they also can interact with I-A b molecules [6,20]. It has been shown that DOTCR is expressed predominantly on CD4 + CD8 -T cells bearing conventional TCR complex in H-2 d mice (DOTG dd mice) [21].…”

Section: Altered Development Of Cd4 + Dotcr + T Cells Bearing Alternamentioning

confidence: 99%

“…T cells bearing alternative TCR complexes along with other structures are also present in mice, which contain the Fc 4 R + chain (FcR + ) and form FcR + -FcR + homodimers or FcR + -´heterodimers rather thań´h omodimers [3][4][5]. In normal mice, alternative TCR complexes are expressed on some unique population of T cells [6][7][8]. Interestingly, expression of TCR § g chains at early stages during thymocyte development can result in expression of alternative rather than conventional TCR complexes on T cells [9].…”

Section: Introductionmentioning

confidence: 99%

“…In addition, T cells from some autoimmune disease patients also express alternative TCR complexes [10]. The alternative TCR complexes are generally expressed at lower levels on those T cells than are conventional TCR complexes expressed on other T cells [6,8].…”

Section: Introductionmentioning

confidence: 99%

“…Second, some of these cells react aberrantly in response to stimulation. For example, the CD8 § § + gut intraepithelial lymphocytes (IEL) are hyporeactive to T cell mitogens [6,12]. Interestingly, some of the gut IEL and CD4 -CD8 -T cells can develop in lck-deficient mice (lckKO mice), suggesting that a different signaling pathway may be involved in these cells [15,16].…”

Section: Introductionmentioning

confidence: 99%

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Development of T cells expressing an altered TCR complex

et al. 2003

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Normal mouse T cells may express alternative TCR complexes containing the Fc 4 R + chain (FcR + ) rather than the´homodimer that is present in conventional TCR complexes. While these T cells could play critical roles in regulating immunity, the role of alternative TCR complexes and their requirement for signaling molecules in T cell development remains unknown. We show that expression of an FcR + transgene in´chain-deficient mice (FcR + TG, KO mice) reduced the percentage and number of CD4 + T cells present in these animals, when compared to C57BL/6 mice. Further studies of FcR + TG,´KO mice expressing the DO11.10 TCR (DOTCR) transgene showed that, when compared to mice expressing conventional TCR complexes, the development of CD4 + , DOTCR + thymocytes was altered in mice of different MHC backgrounds and required the presence of zeta-associated protein (ZAP)-70 and lck kinases. The CD4 + , DOTCR + T cells bearing alternative TCR complexes have impaired Ca 2+ flux and proliferative response to stimulation. Altogether, these results suggest that the altered development of CD4 + T cells is not due to qualitative differences in TCR-mediated signals, but more consistent with the hypothesis that it is due to reduced signaling strength mediated through the FcR + chain containing only one immunoreceptor tyrosine-based activation motif.

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Section: Discussionmentioning

confidence: 99%

Section: Altered Development Of Cd4 + Dotcr + T Cells Bearing Alternamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Development of T cells expressing an altered TCR complex

et al. 2003

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Lineage-specific differences among CD8+ T cells in their dependence of NF-κB/Rel signaling

et al. 1999

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Whereas most CD8+ T cells in lymph nodes and spleen express the CD8α β heterodimer and depend absolutely on thymic competence for their development, a substantial population of T cells expressing CD8α α matures extrathymically. Although the existence of these CD8 sublineages is well established, relatively little is known about differences that might exist among CD8 cells in their requirement for particular transcriptional pathways during the development and maintenance of normal populations. Transgenic mice whose T lineage expresses an IκBα mutant exhibited decreased NF‐κB signaling and a diminution in mature CD8 T cells. We now have determined that although TCR‐dependent CD69 induction by CD8α α and CD8α β T cells was unaffected by inhibition of NF‐κB, TCRα β CD8α β T cells were preferentially reduced compared to their TCRα β CD8α α or TCRγ δ counterparts. This finding was most prominent in spleen, but was also apparent in Peyer's patches of transgenic mice. In addition, diminished antiviral cytotoxic responses of CD8α β intraepithelial lymphocytes were observed after enteric reovirus infection. Taken together, these results indicate that NF‐κB signaling is more important for the thymus‐dependent TCRα β CD8α β population than for other CD8 lineages, and thus regulates the number, function, and normal balance of CD8 subsets in the periphery.

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Lineage-specific differences among CD8+ T cells in their dependence of NF-κB/Rel signaling

Mora¹,

Chen²,

Boothby³

et al. 1999

Eur. J. Immunol.

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Whereas most CD8 + T cells in lymph nodes and spleen express the CD8 § g heterodimer and depend absolutely on thymic competence for their development, a substantial population of T cells expressing CD8 § § matures extrathymically. Although the existence of these CD8 sublineages is well established, relatively little is known about differences that might exist among CD8 cells in their requirement for particular transcriptional pathways during the development and maintenance of normal populations. Transgenic mice whose T lineage expresses an I O B § mutant exhibited decreased NF-O B signaling and a diminution in mature CD8 T cells. We now have determined that although TCR-dependent CD69 induction by CD8 § § and CD8 § g T cells was unaffected by inhibition of NF-O B, TCR § g CD8 § g T cells were preferentially reduced compared to their TCR § g CD8 § § or TCR + ˇ counterparts. This finding was most prominent in spleen, but was also apparent in Peyer's patches of trans-genic mice. In addition, diminished antiviral cytotoxic responses of CD8 § g intraepithelial lymphocytes were observed after enteric reovirus infection. Taken together, these results indicate that NF-O B signaling is more important for the thymus-dependent TCR § g CD8 § g population than for other CD8 lineages, and thus regulates the number, function, and normal balance of CD8 subsets in the periphery.

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Abnormal T cell development in CD3-zeta-/- mutant mice and identification of a novel T cell population in the intestine.

Cited by 176 publications

References 75 publications

Development of T cells expressing an altered TCR complex

Development of T cells expressing an altered TCR complex

Lineage-specific differences among CD8+ T cells in their dependence of NF-κB/Rel signaling

Lineage-specific differences among CD8+ T cells in their dependence of NF-κB/Rel signaling

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