Both CD4+ and CD8+ cells participate in the T helper1/T helper 2 paradigm

Both CD4+ and CD8+ cells participate in the T helper1/T helper 2 paradigm. There is increasing evidence that Th2-like CD8+ cells exist in both humans and mice, and can be derived under similar conditions. IL-12 and IFN-g facilitate differentiation of Th1 or cytotoxic type 1 (Tc1) CD8+ T cells, whereas IL-4 facilitates differentiation into Th2 or cytotoxic type 2 (Tc2) CD8+ T cells.

However, in order for these CD8+ Tc2 cells to become IL-4 secreting, they need to be exposed to require higher levels of IL-4 during the initial priming than do CD4+ Th2 cells. Once committed to a Tc2 lineage, these CD8+ cells secrete the Th2 cytokines IL-4, 5, 9, 10, and 13. Different types of infectious organisms can affect which subsets of CD8+ cells will predominate during an immune response to that infection. Tc2-like cells have been isolated from patients with lepromatous leprosy, human immunodeficiency virus (HIV), and Job syndrome. In contrast, Tc1-like cells have been isolated from patients with tuberculoid leprosy. Although the Tc2 cells function in a “helper” manner, by secreting the appropriate cytokines, they can be just as cytotoxic as Tc1 cells. Both cell subsets kill via Ca2+/perforin-dependent mechanisms and by activation of Fas. Although Tc2 cells can help B cells, they do not do so in a cognate manner. Cognate help by Tc2 cells is unlikely because these cells do not recognize antigen processed and presented by MHC class II cells, as Tc2 cells are restricted to recognizing MHC class I. However, it is possible that Tc2 cells can help B cells via bystander, or non-cognate mechanisms.