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

Charles B. Stephensen, Alexander D Borowsky, Kevin C K Lloyd

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

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-α 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-γ 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.

Original languageEnglish (US)
Pages (from-to)484-498
Number of pages15
JournalImmunology
Volume121
Issue number4
DOIs
StatePublished - Aug 2007

Keywords

  • Knockout mice
  • Retinoid X receptor-α
  • T helper type 1/T helper type 2
  • T lymphocyte
  • Vitamin A

ASJC Scopus subject areas

  • Immunology

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