SPONTANEOUS LYMPHOCYTE-PROLIFERATION IN HUMAN T-CELL LYMPHOTROPIC VIRUS TYPE-I (HTLV-I) AND HTLV-II INFECTION - T-CELL SUBSET RESPONSES AND THEIR RELATIONSHIPS TO THE PRESENCE OF PROVIRUS AND VIRAL-ANTIGEN PRODUCTION

Spontaneous lymphocyte proliferation (SLP) during in vitro culture of mononuclear cells (MCs) characterizes over half of asymptomatic individuals infected,vith human T-cell lymphotropic virus type I (HTLV-I) or HTLV-II. Both CD4 and CD8 T-cell subsets within MC cultures are activated during SLP, as judged by high-density CD25 (CD25(bright)) expression; it is unclear, however, whether both cell subsets can directly undergo SLP. In the present investigation, the SLP capacities of purified CDS and CD4 cells were examined in subjects infected with HTLV-I (n = 19) or HTLV-II (n = 54) in relation to the SLP status of MCs from each subject. No increase in SLP was observed for CD8 or CD4 cells from SLP-negative (SLP(-)) HTLV-infected subjects, whereas robust SLP characterized CD4 cells from all SLP-pgsitive (SLP(+)) individuals, regardless of HTLV type. In contrast, SLP(+) CD4 cells characterized only 23% (7 of 31) of HTLV-II+ SLP(+) individuals, whereas SLP(+) CD4 cells characterized 100% of HTLV-I+ SLP(+) individuals. In cocultures of HTLV-II+ SLP(+) CD8 cells and autologous SLP(-) CD4 cells, sizable proportions of both CD8 cells and CD4 cells coexpressed CD25(bright), suggesting that SLP(-) CD4 cells were activated in the presence of SLP(+) CD8 cells. PCR analysis for tax sequences detected provirus in most CD4- and CD8-cell preparations from HTLV-seropositive individuals, regardless of type and the SLP status of cell subsets. To determine whether SLP was associated with activation of viral genes, levels of HTLV-I and HTLV-II core antigen (Ag) in supernatants were measured. Viral Ag production and SLP responses were significantly correlated for both CD4 and CD8 cells in both HTLV-I and HTLV-II infections. However, inhibition of CD8- or CD4-cell SLP by cyclosporin A or anti-Tac (anti-CD25) did not reduce Ag production, indicating that Ag production is not coupled to SLP. These findings show that CD4 cells from SLP(+) HTLV-I+ and SLP(+) HTLV-II+ individuals differ in SLP capacity, that the absence of SLP does not indicate a lack of infection, and that production of viral Ag is associated with, but not dependent on, SLP.