Disruption of Rxra gene in thymocytes and T lymphocytes modestly alters lymphocyte frequencies, proliferation, survival and T helper type 1/type 2 balance.

Disruption of Rxra gene in thymocytes and T lymphocytes modestly alters lymphocyte frequencies, proliferation, survival and T helper type 1/type 2 balance. Research Abstract Details 

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Disruption of Rxra gene in thymocytes and T lymphocytes modestly alters lymphocyte frequencies, proliferation, survival and T helper type 1/type 2 balance. Abstract Text:

Charles B Stephensen,Alexander D Borowsky,Kevin C Kent Lloyd,

Retinoid X receptor (RXR) agonists, including the vitamin A metabolite 9-cis retinoic acid, decrease T-lymphocyte apoptosis and promote T helper type 2 (Th2) development ex vivo. To examine the in vivo role of RXR-alpha in T-lymphocyte development and function, we disrupted the Rxra gene in thymocytes and T lymphocytes using cyclization recombinase (Cre)-loxP-mediated excision of Rxra exon 4. Expression of Cre was targeted to these cells using the Lck promoter. Successful disruption of exon 4 was seen in thymus and T lymphocytes. Mice were healthy and the thymus, spleen and lymph nodes appeared normal. However, knockout mice had a lower percentage of double-positive (CD4(+) CD8(+)) and a higher percentage of double-negative thymocytes than wild-type mice. The percentage of splenic B lymphocytes was lower in unimmunized and ovalbumin-immunized knockout mice and the percentage of T lymphocytes was lower in immunized knockout mice. Ex vivo proliferation was decreased and apoptosis was increased in T lymphocytes from knockout mice. Memory CD4(+) T lymphocytes from knockout mice produced more interferon-gamma and interleukin-2 (IL-2) and less IL-5 and IL-10 than memory cells from wild-type mice, indicating a Th1 bias in vivo. However, Rxra disruption did not similarly bias ex vivo differentiation of naive CD4(+) T lymphocytes, nor did Rxra disruption alter the serum immunoglobulin G1/immunoglobulin G2a response to immunization. In summary, disruption of Rxra altered the percentages of T and B lymphocytes, produced a Th1 bias in vivo, and altered T-lymphocyte proliferation and apoptosis ex vivo. These differences were modest in magnitude and their impact on disease resistance is yet to be examined.

Disruption of Rxra gene in thymocytes and T lymphocytes modestly alters lymphocyte frequencies, proliferation, survival and T helper type 1/type 2 balance. Publishing Authors By Initials

CB Stephensen,AD Borowsky,KC Lloyd,

For similar cells: cells, cultured: tumor cells, cultured research abstracts see: cells: cells, cultured: tumor cells, cultured research

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Disruption of Rxra gene in thymocytes and T lymphocytes modestly alters lymphocyte frequencies, proliferation, survival and T helper type 1/type 2 balance. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Immunology

VOLUME: 121

Page Numbers: 484-98

Journal Abbreviation: Immunology

ISSN: 0019-2805

DAY: 13

MONTH: 04

YEAR: 2007

Disruption of Rxra gene in thymocytes and T lymphocytes modestly alters lymphocyte frequencies, proliferation, survival and T helper type 1/type 2 balance. Information

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LANGUAGE: eng

NlmUniqueID: 374672

Disruption of Rxra gene in thymocytes and T lymphocytes modestly alters lymphocyte frequencies, proliferation, survival and T helper type 1/type 2 balance. Keywords Mesh Terms:

KEYWORDS: Tumor Cells, Cultured

MESH TERMS: immunology

Chemical & Substance for Abstract: Disruption of Rxra gene in thymocytes and T lymphocytes modestly alters lymphocyte frequencies, proliferation, survival and T helper type 1/type 2 balance. Information

Substance Name: Retinoid X Receptor alpha

Registry Number: 0

Grant and Affiliation Information for Disruption of Rxra gene in thymocytes and T lymphocytes modestly alters lymphocyte frequencies, proliferation, survival and T helper type 1/type 2 balance.

AFFILIATION: USDA Western Human Nutrition Research Center and Nutrition Department, University of California, Davis, CA 95616, USA. cstephen@whnrc.usda.gov

Country: England

AGENCY: United States NIAID

GRANT: R01 AI 50863

ACRONYM: AI

MEDLINETA: Immunology

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