Activation of CD4 T cells by somatic transgenesis induces generalized immunity of uncommitted T cells and immunologic memory

Cellular immune responses were analyzed in vivo after a single intraspleen inoculation of DNA coding for a 12-residue Th cell determinant associated w ith a 12-residue B cell epitope, a process termed somatic transgene immuniz ation. We show that CD4 T cells are readily activated and produce IL-2, IFN -gamma and IL-4, characteristics of an uncommitted phenotype, Linked recogn ition of the tao epitopes coded in the same transgene promoted IgM-IgG1 swi tch and enhanced the total Ab response but had no effect on IgG2a Abs, Alth ough originating in the spleen, T cell responsiveness was found to spread i mmediately and with similar characteristics to all lymph nodes in the body. A single inoculation was also effective in establishing long term immunolo gic memory as determined by limiting dilution analysis, with memory T cells displaying a cytokine profile different from that of primary effector T ce lls. These studies provide evidence that by initiating immunity directly in secondary lymphoid organs, an immune response is generated with characteri stics that differ from those using vaccines of conventional DNA or protein in adjuvant administered in peripheral sites. Somatic transgene immunizatio n can therefore be used to probe T cell responsiveness in vivo and represen ts a tool to further understanding of the nature of the adaptive immune res ponse.