Altered HLA antigens expressed on T and B lymphocytes of adult T‐cell leukemia/lymphoma patients and their relatives

Abstract

The HLA types of peripheral blood lymphocytes (PBL) of 36 adult T-cell leukemia/lymphoma (ATLL) patients were examined and compared with those of 45 healthy relatives of these patients, and with those of 10 non-ATLL families including 80 healthy members. Thirty-one percent of ATLL patients showed either a gain or a loss of HLA antigens determined by the presence of alien HLA antigens or the absence of inherent HLA antigens deduced from familial haplotype analysis. The antigen specificity of HLA gained or lost was variable and differed from case to case among ATLL patients. Although the gain of HLA was detected only in ATLL patients, the loss of HLA was found both in ATLL patients and in asymptomatic healthy relatives. The rate of HLA loss in ATLL patients (8.4%) and their relatives (17.8%) was much higher than in relatives of non-ATLL patients (1.1%). The HLA gain and loss revealed in the PBL of ATLL patients were confirmed by altered HLA phenotypes in the cloned T and B cells established from ATLL patients. Our results suggest that latently infecting HTLV-I may induce altered HLA phenotypes in T and B cells, primarily with loss of HLA antigens in a population of asymptomatic virus carriers, and secondarily with a gain of HLA antigens after the development of ATLL.

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

“…In agreement with this idea, It was reported that peripheral mononuclear lymphocytes isolated from ATL patients had altered HLA expression on the cell surface (52). Moreover, Sonoda et al demonstrated the possibility of loss of HLA antigens in a population of asymptomatic HTLV-1 carriers and a gain in their cell surface after the development of ATL (49). Thus, the rat model system presented here will be a useful tool with which to further (41).…”

Human T-Cell Leukemia Virus Type 1 (HTLV-1) p12IDown-Modulates ICAM-1 and -2 and Reduces Adherence of Natural Killer Cells, Thereby Protecting HTLV-1-Infected Primary CD4+T Cells from Autologous Natural Killer Cell-Mediated Cytotoxicity despite the Reduction of Major Histocompatibility Complex Class I Molecules on Infected Cells

“…One reason for the persistence of HTLV-1 in the host may be a consequence of the ability of the virus to evade the host immune response. A possible mechanism by which HTLV-1 evades immune responses is by down-modulating the expression of major histocompatibility complex class I (MHC-I) molecules on the surface of infected cells allowing their escape from recognition and destruction by HTLV-1 antigen-specific cytotoxic T lymphocytes (CTLs) (55,68,73). The HTLV-1 accessory protein p12 I has been previously shown to down-modulate the surface expression of MHC-I on T-cell lines (38).…”

“…Although uninfected cells may express these activating ligands, NK cells are unable to destroy these cells because MHC-I on the surface of uninfected cells engage specific inhibitory receptors (iNKRs) dampening NK cell cytotoxicity (12,15,22,27). Whether down-modulation of MHC-I leads to NK cell cytotoxicity toward HTLV-1-infected lymphocytes is not yet clearly defined (64,68,73).…”

Free Major Histocompatibility Complex Class I Heavy Chain Is Preferentially Targeted for Degradation by Human T-Cell Leukemia/Lymphotropic Virus Type 1 p12IProtein

“…In the case of HTLV-1, alterations in HLA expression on the cell surface have been demonstrated in peripheral mononuclear lymphocytes isolated from patients with adult T-cell leukemia, as well as in HTLV-1-infected cell lines (28,47,51). A loss of HLA antigens on the surface of cells from asymptomatic carriers and a gain in their cell surface expression after the development of ATLL has also been suggested (47).…”

“…A loss of HLA antigens on the surface of cells from asymptomatic carriers and a gain in their cell surface expression after the development of ATLL has also been suggested (47). Ec-topically expressed Tax, the viral transactivator, has also been shown to increase MHC-I expression on the surface of transfected glial cells (44), an event that could contribute to escape from NK cells (51).…”