Anti‐HTLV‐1 tax antibody and tax‐specific cytotoxic T lymphocyte are associated with a reduction in HTLV‐1 proviral load in asymptomatic carriers

Abstract

Previous studies have suggested that higher anti-human T-lymphotropic virus 1 (HTLV-1) antibody titer and lower anti-HTLV-1 Tax antibody reactivity are risk factors for adult T-cell leukemia/lymphoma. In the present study, we analyzed the relationships between these factors and clarified their significance. Forty-five carriers were examined for anti-HTLV-1 and anti-Tax antibody by ELISA. In addition, 43 of the 45 carriers with HLA-A*0201 and/or A*2402 were examined for frequency of Tax-specific cytotoxic T lymphocytes (CTLs) using HTLV-1/HLA tetramers, and 44 were examined for proviral load by real-time PCR. The relationships between these factors were analyzed statistically. The frequencies of Tax11-19 and Tax301-309-specific CTLs were significantly higher in the anti-Tax antibody-positive group as compared with the antibody-negative group (P = 0.002 and 0.033, respectively). Anti-HTLV-1 antibody titer had a positive correlation with proviral load (P = 0.019), whereas anti-Tax antibody did not show a significant correlation. Higher frequencies of both Tax11-19 and Tax301-309-specific CTLs are related to a reduction in proviral load (P = 0.017 and 0.015, respectively). Synergistic interactions of humoral and cellular immunity against Tax protein were demonstrated in HTLV-1 carriers. Tax-specific CTL may reduce HTLV-1 proviral load to prevent asymptomatic carriers from developing adult T-cell leukemia/lymphoma.

An animal model of adult T-cell leukemia: humanized mice with HTLV-1–specific immunity

“…[42][43][44] To investigate whether Tax-specific CTLs were induced in HTLV-1-infected mice, the IBMI-huNOG mice were generated using hematopoietic stem cells purified from the cord blood of an HLA-A*24:02 haplotype individual. HLA-A*24:02 tetramers coupled with Tax301-309 were used to detect CTLs.…”

New Strategy of Adult T-cell Leukemia Treatment Targeted for Anti-tumor Immunity and a Longevity Gene-encoded Protein

“…This study demonstrates the importance of CD8 ＋ T-cells recognizing HTLV-1 Envtetramers in HAM/TSP patients and CCs, thereby suggesting that the diversity, frequency and repertoire of HTLV-1 Env-speciˆc CD8 ＋ T-cell clones may be related to the hyperimmune response in HAM/TSP and CCs, although diŠerent immunological mechanisms may mediate the hyperimmunity in these conditions. 36,37) Dysfunction of HTLV-1-speciˆc CD8＋ T-cell in ATL Patients via the PD-1/PD-L1 Pathway T cell receptor costimulatory pathways assist in regulating T cell activation and tolerance. 38 40) The B7-CD28 superfamily membership has been expanded to include costimulatory and inhibitory T cell receptors, including CD28 and programmed death-1 (PD-1).…”

NK314 potentiates antitumor activity with adult T-cell leukemia-lymphoma cells by inhibition of dual targets on topoisomerase IIα and DNA-dependent protein kinase

“…Based on these studies, targeting therapies for various molecules, such as Tax, NF-B, Akt/PKB, mTOR, CD25, CD52, and chemokine receptor-4, have been developed under clinical or preclinical investigations using small molecules or monoclonal antibodies. [12][13][14][15][16][17][18][19][20][21][22][23] The DNA repair system is also a promising target for sensitization of cancer treatment. [24][25][26] Although genetic instability of proliferating cells is necessary for most cell types to become malignant, cells that are overly unstable genetically will die.…”