Private specificities of CD8 T cell responses control patterns of heterologous immunity

Kim, Sung-Kwon; Cornberg, Markus; Wang, Xiaoting Z.; Chen, Hong D.; Selin, Liisa K.; Welsh, Raymond M.

The significance of this work is in the understanding of the basic concepts of heterologous immunity. The replication of VV is reduced in LCMV-immune mice in comparison to naive mice, and T cell-dependent immunopathology is more dramatic. Adoptive transfer studies have shown that both the protective immunity and the immunopathology are dependent on T cells and on IFN-␥ production (1). It is noteworthy that IFN-␥ can be detected in vivo in different proportions of T cells of each tested LCMV epitope specificity (NP396, GP33, GP34, and NP205) by 3 d after infection, when viral titers are being controlled (3). It is not clear whether this IFN-␥ production is a consequence of T cell cross-reactivity or a nonspecific cytokine effect (28, 29) . As the infection progresses, T cells of distinct LCMV-epitope specificities expand. Given the pervasive nature of T cell cross-reactivity and the fact that it takes a stronger TCR signal to stimulate proliferation than IFN-␥ production (30) , all of these events could be determined by cross-reactivity, but this is in need of further study.