Regulation of the expression of MHC class I and II by class II transactivator (CIITA) in hematopoietic cells

Liu, AC Takahashi, M Toba, K Zheng, ZY Hashimoto, S Nikkuni, K Furukawa, T Koike, T Aizawa, Y

Ac. Liu et al., Regulation of the expression of MHC class I and II by class II transactivator (CIITA) in hematopoietic cells, HEMATOL ONC, 17(4), 1999, pp. 149-160

21

INGLESE

Article

Onconogenesis & Cancer Research

HEMATOLOGICAL ONCOLOGY

0278-0232 → ACNP

17

4

1999

149 - 160

ISI

0278-0232(199912)17:4<149:ROTEOM>2.0.ZU;2-I

In order to develop an effective immunotherapy for hematological malignanci es, we investigated the applicability of class II transactivator (CIITA), w hich had been demonstrated to regulate the expression of MHC class IT (MHC- II) by assembling the transcription factors of MHC-II molecules, for immuno therapy by potentiating the antigenicity of tumour cells by inducing MHC ex pression. First, 32 hematopoietic cell lines were analysed for the expressi on of HLA-DR, CIITA, RFX5 or HLA-ABC. Fourteen cell lines were positive and 18 were negative for HLA-DR. AU the 14 HLA-DR positive cell lines were dem onstrated to express CIITA mRNA by RT-PCR. On the other hand, in all the 18 HLA-DR negative cell lines, the expression of CIITA was not demonstrated. RFX5, which is one of the transcription factors of MHC-IT, was expressed ub iquitously in all 32 cell lines. Three cell lines out of 23 hematopoietic c ell lines examined were negative for HLA-ABC, and all three of these cell l ines were negative for both HLA-DR and CIITA expression. Furthermore, CIITA cDNA was transfected into K562 cells, which were negative for HLA-ABC, -DR and -DQ, but positive for HLA-DP. The transfection rendered HLA-DR negativ e to positive and increased the expression level of HLA-DP, but HLA-DQ rema ined negative. In addition to HLA-DR, HLA-ABC was also induced to express b y the transfection of CIITA gene. The present study demonstrated that the e xpression of HLA-DR in hematopoietic cells is regulated in subordination to CIITA and the expression of HLA-DR (and HLA-ABC in K562) is induced by tra nsfection with the CIITA gene. These findings revealed the applicability of CIITA in potentiating antitumour immunity of HLA-DR negative tumour cells for immunotherapy of hematological malignancies. Copyright (C) 1999 John Wi ley & Sons, Ltd.