Correlation of major histocompatibility complex class I downregulation with resistance of human T-cell leukemia virus type 1-infected T cells to cytotoxic T-lymphocyte killing in a rat model.
Human T-cell leukemia virus type 1 (HTLV-1) causes adult T-cell leukemia (ATL) in infected individuals after a long incubation period. Despite the apparent transforming ability of HTLV-1 under experimental conditions, most HTLV-1 carriers are asymptomatic. These facts suggest that HTLV-1 is controlled by host immunity in most carriers. To understand the interplay between host immunity and HTLV-1-infected cells, in this study, we isolated several HTLV-1 Tax-specific cytotoxic T-lymphocyte (CTL) lines from rats inoculated with Tax-coding DNA and investigated the long-term effects of the CTL on syngeneic HTLV-1-infected T cells. Our results demonstrated that long-term mixed culture of these CTL and the virus-infected T cells led to the emergence of CTL-resistant HTLV-1-infected cells. Although the Tax expression level in these resistant cells was equivalent to that in the parental cells, expression of surface major histocompatibility complex class I (MHC-I) was significantly downregulated in the resistant cells. Downregulation of MHC-I was more apparent in RT1.A(l), which presents a Tax epitope recognized by the CTL established in this study. Moreover, peptide pulsing resulted in killing of the resistant cells by CTL, indicating that resistance was caused by a decreased epitope density on the infected cell surface. This may be one of the mechanisms for persistence of HTLV-1-infected cells that evade CTL lysis and potentially develop ATL.
Ohashi
Takashi
T
Department of Immunotherapeutics, Tokyo Medical and Dental University, Medical and Dental Research Division, Tokyo 113-8519, Japan. toha.impt@tmd.ac.jp
Hanabuchi
Shino
S
Suzuki
Reiko
R
Kato
Hirotomo
H
Masuda
Takao
T
Kannagi
Mari
M
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D006800:Deltaretrovirus Infections / Q000276:immunology* / Q000821:virology; D004195:Disease Models, Animal; D015536:Down-Regulation; D000939:Epitopes; D005260:Female; D016356:Gene Products, tax / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D015368:Human T-lymphotropic virus 1 / Q000276:immunology; D006801:Humans; D008969:Molecular Sequence Data; D051381:Rats; D011916:Rats, Inbred F344; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000939:Epitopes; D016356:Gene Products, tax; D015395:Histocompatibility Antigens Class I