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Prepublished online as a Blood First Edition Paper on December 27, 2002; DOI 10.1182/blood-2002-06-1855.

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Blood, 1 May 2003, Vol. 101, No. 9, pp. 3550-3559

IMMUNOBIOLOGY

Promoter IV of the class II transactivator gene is essential for positive selection of CD4+ T cells

Jean-Marc Waldburger, Simona Rossi, Georg A. Hollander, Hans-Reimer Rodewald, Walter Reith, and Hans Acha-Orbea

From the Institute of Biochemistry and Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Epalinges, Switzerland; Department of Genetics and Microbiology, University of Geneva, Medical School, Geneva, Switzerland; Pediatric Immunology, Departments of Research and Clinical-biological Sciences, and the Children's Hospital, University of Basel, Switzerland; Department for Immunology, University Clinics Ulm, Germany.

Major histocompatibility complex class II (MHCII) expression is regulated by the transcriptional coactivator CIITA. Positive selection of CD4+ T cells is abrogated in mice lacking one of the promoters (pIV) of the Mhc2ta gene. This is entirely due to the absence of MHCII expression in thymic epithelia, as demonstrated by bone marrow transfer experiments between wild-type and pIV-/- mice. Medullary thymic epithelial cells (mTECs) are also MHCII- in pIV-/- mice. Bone marrow-derived, professional antigen-presenting cells (APCs) retain normal MHCII expression in pIV-/- mice, including those believed to mediate negative selection in the thymic medulla. Endogenous retroviruses thus retain their ability to sustain negative selection of the residual CD4+ thymocytes in pIV-/- mice. Interestingly, the passive acquisition of MHCII molecules by thymocytes is abrogated in pIV-/- mice. This identifies thymic epithelial cells as the source of this passive transfer. In peripheral lymphoid organs, the CD4+ T-cell population of pIV-/- mice is quantitatively and qualitatively comparable to that of MHCII-deficient mice. It comprises a high proportion of CD1-restricted natural killer T cells, which results in a bias of the Vbeta repertoire of the residual CD4+ T-cell population. We have also addressed the identity of the signal that sustains pIV expression in cortical epithelia. We found that the Jak/STAT pathways activated by the common gamma  chain (CD132) or common beta  chain (CDw131) cytokine receptors are not required for MHCII expression in thymic cortical epithelia.

© 2003 by The American Society of Hematology.
 

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