CD4+ Th1 and CD8+ Type 1 Cytotoxic T Cells Both Play a Crucial Role in the Full Development of Contact Hypersensitivity

Abstract

The role of CD4+ vs CD8+ T cells in contact hypersensitivity (CHS) remains controversial. In this study, we used gene knockout (KO) mice deficient in CD4+ or CD8+ T cells to directly address this issue. Mice lacking either CD4+ or CD8+ T cells demonstrated depressed CHS responses to dinitrofluorobenzene and oxazolone compared with wild-type C57BL/6 mice. The depression of CHS was more significant in CD8 KO mice than in CD4 KO mice. Furthermore, in vivo depletion of either CD8+ T cells from CD4 KO mice or CD4+ T cells from CD8 KO mice virtually abolished CHS responses. Lymph node cells (LNCs) from hapten-sensitized CD4 and CD8 KO mice showed a decreased capacity for transferring CHS. In vitro depletion of either CD4+ T cells from CD8 KO LNCs or CD8+ T cells from CD4 KO LNCs resulted in a complete loss of CHS transfer. LNCs from CD4 and CD8 KO mice produced significant amounts of IFN-γ, indicating that both CD4+ and CD8+ T cells are able to secrete IFN-γ. LNCs from CD8, but not CD4, KO mice were able to produce IL-4 and IL-10, suggesting that IL-4 and IL-10 are mainly derived from CD4+ T cells. Intracellular cytokine staining of LNCs confirmed that IFN-γ-positive cells consisted of CD4+ (Th1) and CD8+ (type 1 cytotoxic T) T cells, whereas IL-10-positive cells were exclusively CD4+ (Th2) T cells. Collectively, these results suggest that both CD4+ Th1 and CD8+ type 1 cytotoxic T cells are crucial effector cells in CHS responses to dinitrofluorobenzene and oxazolone in C57BL/6 mice.

Th1 and Type 1 Cytotoxic T Cells Dominate Responses in T-bet Overexpression Transgenic Mice That Develop Contact Dermatitis

“…There have been major controversies on the respective roles of CD4 ϩ and CD8 ϩ T cells in the development of CHS inflammatory reactions (12). However, it has become clear that both CD4 ϩ and CD8 ϩ T cells can act as effector cells in this context (17). Wang et al (17) showed that both CD4 ϩ Th1 and CD8 ϩ Tc1 cells are crucial effectors in the CHS response to DNFB.…”

“…However, it has become clear that both CD4 ϩ and CD8 ϩ T cells can act as effector cells in this context (17). Wang et al (17) showed that both CD4 ϩ Th1 and CD8 ϩ Tc1 cells are crucial effectors in the CHS response to DNFB. Previous studies have also demonstrated that cytokines play important effector and regulatory roles in CHS responses.…”

“…Some investigations in mice found CHS to be associated with CD4 ϩ T lymphocyte function and to be compromised when such cells were deleted (15,16). However, there is growing evidence that in many instances the predominant effector cell in CHS may be a CD8 ϩ T lymphocyte (13,17,18). Wang et al (17) clearly demonstrated that the deletion of CD8 ϩ Tc1 cells had a more significant suppressive effect than the deletion of CD4 ϩ Th1 cells in CHS responses to 2,4-dinitrofluorobenzene (DNFB).…”

Allergic contact dermatitis: the cellular effectors

“…Although this rather polarized model is attractive, there may in practice be a requirement for both CD4 π and CD8 π T lymphocytes for the initiation and maintenance of a complete immune response to skin sensitizing chemicals. Certainly this is the implication from the results of recent studies performed in mice by Wang et al (30). On the basis of secondary depletion experiments from CD4 and CD8 knockout animals, they concluded both CD4 π Th1 cells and CD8 π Tc1 cells are required for the full development of contact hypersensitivity (30).…”

“…Certainly this is the implication from the results of recent studies performed in mice by Wang et al (30). On the basis of secondary depletion experiments from CD4 and CD8 knockout animals, they concluded both CD4 π Th1 cells and CD8 π Tc1 cells are required for the full development of contact hypersensitivity (30). This is despite the fact that in some cases it appears possible to generate CD8 π T lymphocyte responses to skin sensitizing chemicals in the absence of antigen-activated CD4 π cells (28,31).…”