The functional role of CD8+ T helper type 2 cells

T he seminal discovery by Mosmann and Coffman (1) that long-term CD4 + T cell clones could be segregated into subsets that produce distinct types of cytokines opened the way for extensive study of how these subsets are generated and what role they play in immune regulation as it relates to disease. Following this observation it quickly became evident in a murine model of Leishmaniasis that CD4 + T cells from mice that produced a Thl response characterized by production of IFN-qr were cured, while mice expressing a Th2 response characterized by II.,4 production were susceptible to disease (2). These studies established that functional T helper subsets existed in vivo. After these observations several groups became interested in the mechanism by which naive CD4 + T ceils differentiated into Thl or Th2 type cells. From these studies it became clear that lymphokines themselves exert a powerful regulatory influence on this process (3, 4). Moreover, I1:4 was shown to be required for Th2 differentiation whereas I1:12 strikingly enhances the process of Thl development. These in vitro studies formed the basis of similar types of experiments with CD8 + T cells. The recent reports documenting the ability of CD8 T cells to develop activities normally associated with CD4 + Th2 lym-phocytes encourage us to suggest the mechanism whereby CD8 + T cells are involved in immune regulation. Development of CD8 + Th2 Cells In Vitro In an early study it was demonstrated that naive CD8 + T ceils cultured in vitro on anti-CD3-coated dishes in the presence of I1:4, developed into CD8 T cells that produced I1:4 upon restimulation (5). These findings were extended by Erard et al. (6) using mitogens or allostimulation in the presence of I1:4 to demonstrate that the CD8 T cells not only switched to I1:4, I1:5, and I1:10 production but lost the potential for IFN-3"/I1:2 production and cytotoxic activity. Also the CD8 cells were found to be able to help B cells to antibody production through the expression of the CD40L. The article in a recent issue of The Journal of Experimental Medicine by Croft et al. (7) extends this phenomenon to more physiological antigens by studying the outcome of priming for CD8 § T cells using cells from mice transgenic for an TClk-od[3 that recognizes H-Y on Db. These workers demonstrated that by activating CD8 + T cells in the presence of I1:2 or I1:12 for …