This projects seeks to understand the immunologic basis for the epidemiological outcome observation of an increased incidence of bacterial pneumonia in HTLV-II-infected blood donors. In a study of persons with both HTLV-II seropositivity and intravenous drug use, an increased risk for bacterial pneumonia compared to patients with neither risk was found. A similar finding of increased risk for bacterial pneumonia in HTLV-II-infected individuals was observed in a clinical outcome analysis of blood donors who participated in a Retroviral Epidemiological Donors Study. Since the cell tropism of HTLV-II infection includes CD4+ and CD8+ T cells, B cells and monocytes, the investigators will determine whether HTLV-II infection predisposes to bacterial pneumonia by creating immune dysfunction in these cells which are known to be critical for natural protection against pneumococcal pneumonia, the most common cause of bacterial pneumonia in individuals with immune dysfunction. Studies planned for the next five years address the immune status of HTLV-II-infected persons. HTLV-II-infected and -uninfected individuals will be vaccinated with the pneumococcal 23-valent polysaccharide vaccine, and their qualitative and quantitative antibody responses will be investigated by determining the isotype and IgG subclass distribution, concentration, avidity and opsonic function of specific pneumococcal capsular antibodies. The same individuals will also be vaccinated with tetanus toxoid protein antigen as a control for antibody response to a separate class of antigen, and their antibody responses measured. The effect of HTLV-II infection of T cells on the proliferative and antibody-secreting functions of B lymphocytes will be tested. CD4+ and CD8+ T cells will be isolated from HTLV-II-infected persons using immunobeads, co-cultivated with normal B lymphocytes, and the functional activity of the B cells assessed using mitogen stimulation and ELISA antibody quantitation assays. Levels of B cell regulatory cytokines produced by infected and uninfected T cells will be measured by ELISA. Levels of immune response markers IL2 receptor on CD8+ T cells, and CD21 and CD35 on B cells will be determined by flow cytometry. The phagocytic and bactericidal function of PMN and of human macrophages derived from the monocytes from HTLV-II-infected individuals will be tested and compared to the function of those cells from uninfected persons. Human CD4+ and CD8+ T cells will be isolated using immunobeads and quantities of macrophage and PMN regulatory cytokines produced by HTLV-II-infected and -uninfected T Cells will be measured by ELISA. The effect of HTLV-II infection of human T cells on cytokine-dependent activation of macrophages and PMN will be studied using functional assays of pneumococcal phagocytic killing.
| Jarvis, Gary A; Janoff, Edward N; Cheng, Hui et al. (2005) Human T lymphotropic virus type II infection and humoral responses to pneumococcal polysaccharide and tetanus toxoid vaccines. J Infect Dis 191:1239-44 |
