Predominant recognition of human T cell leukemia virus type I (HTLV-I) pX gene products by human CD8+ cytotoxic T cells directed against HTLV-I-infected cells

Abstract

We established long-term cell lines of cytotoxic T lymphocytes (CTL) specific for human T cell leukemia virus type I (HTLV-I) from peripheral blood lymphocytes (PBL) of a patient with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), an HTLV-I-carrier with Sjögren syndrome, and an asymptomatic HTLV-I-carrier, by repeated stimulation with autologous HTLV-I-infected T cells in vitro. CTL derived from the patient with HAM/TSP expressed CD8 antigen, and their function was restricted by HLA-A2. They showed cytotoxic effects predominantly against the target cells expressing HTLV-I p40tax among the autologous B cell lines infected with vaccinia recombinants containing various HTLV-I genes which served as targets. These data are consistent with the previously reported findings that fresh PBL of HAM/TSP patients contain p40tax-specific CTL activity. Furthermore, CTL derived from the patient with Sjögren syndrome without neurological involvement also demonstrated cytotoxicity predominantly to p40tax. The cytotoxicity to the target cells experimentally expressing p40tax was blocked by unlabeled HTLV-I-infected cells possessing HLA-A2. HTLV-I-specific cytotoxicity was also inhibited by unlabeled B cells bearing p40tax. Thus, HTLV-I p40tax-specific cytotoxicity is mediated by the major CTL population activated by native HTLV-I antigens in patients with HAM/TSP or Sjögren syndrome. In contrast to the CTL of these patients, CTL similarly induced from the asymptomatic HTLV-I-carrier, which were highly cytotoxic to autologous HTLV-I-infected T cells, did not show significant levels of cytotoxicity to autologous B cells expressing p40tax.(ABSTRACT TRUNCATED AT 250 WORDS)

Reduced Frequency, Diversity, and Function of Human T Cell Leukemia Virus Type 1-Specific CD8+ T Cell in Adult T Cell Leukemia Patients

“…The cultured cells were morphologically activated T cells and clustered in colony formation. We observed increases in the numbers of positive cells corresponding to Tax [11][12][13][14][15][16][17][18][19] in ATL patient and AC (Fig. 3, A and B).…”

“…In contrast, ATL recognized only Tax [11][12][13][14][15][16][17][18][19] with HLA-A*0201 and Tax 301-309 with HLA-A*2402 at frequencies of 30 and 55%, respectively. Among the individual HTLV-1/ HLA tetramers, two (Tax [11][12][13][14][15][16][17][18][19] , p ϭ 0.0042; and Tax 301-309 , p ϭ 0.0031; Table II) were significantly more frequent in AC than ATL. Among AC, 24% of Tax epitopes were positive, whereas significantly fewer epitopes were positive among ATL (9%, p ϭ 0.0004; Table II).…”

“…With regard to Tax 11-19 -specific tetramer binding cells in individual subjects with HLA-A*0201, the frequency of percentage of CD8 ϩ T cells binding Tax [11][12][13][14][15][16][17][18][19] /HLA-A*0201 tetramer in Table II. b Epitopes detected by HTLV-1/HLA tetramers/number of tetramers tested.…”

“…The proviral load of Tax [11][12][13][14][15][16][17][18][19] tetramer-positive AC was significantly lower than that of Tax [11][12][13][14][15][16][17][18][19] tetramer-negative AC (mean Ϯ SE, 38.1 Ϯ 13.8 vs 74.8 Ϯ 8.0; p ϭ 0.043; Table IV). These findings are consistent with Bangham's report (47) and suggest that Tax [11][12][13][14][15][16][17][18][19] CTL works as a strong down-regulator of the proviral load. In contrast, with regard to Tax 301-309 tetramer, there was no significant difference between the proviral load of Tax 301-309 tetramer-positive AC and negative AC (mean Ϯ SE, 72.4 Ϯ 9.4 vs 53.5 Ϯ 11.6; Table IV).…”

“…In contrast, with regard to Tax 301-309 tetramer, there was no significant difference between the proviral load of Tax 301-309 tetramer-positive AC and negative AC (mean Ϯ SE, 72.4 Ϯ 9.4 vs 53.5 Ϯ 11.6; Table IV). The reason why the proviral load of Tax 301-309 tetramer-positive AC was lower than that of negative AC can be explained by the negative group containing many Tax [11][12][13][14][15][16][17][18][19] tetramer-positive AC (7 of 13). Therefore, we omitted HLA-A*02-positive (including HLA-A*0201 and HLA-A*0206) subjects in analysis of Tax 301-309 tetramer.…”