Recent studies shed light on the role of DC involvement in various diseases such as autoimmunity, allergy, transplantation, infection and cancer. For example, studies showed that DCs differentiated in vitro express very important co-stimulatory molecules, e.g. CD40, which allow these cells to approach T cells and deliver signals to them [22, 23]. With respect to that phenomenon, cytokines (e.g., GM-CSF, TNF-α) produced by keratinocytes affect DC differentiation dramatically . Moreover, DCs alone produce essential cytokines (e.g. IL-1β, TNF-α, IL-6), and chemokines MIP-1α, MIP-1γ, IL-15 and IL-8 [9, 36–39]. Some of these cytokines contribute directly to the DCs ability to attract and recruit T cells in sites of inflammation. A number of autoimmune diseases (rheumatoid arthritis) or skin psoriasis demonstrates the accumulation of DCs in diseased tissues . This evidence suggests that DC enrichment within the cytokine-rich synosium or epidermis undergo phenotypic and functional maturation in vivo. Furthermore, it seems that the ligation of CD40 with DCs can enhance the antigen presenting capacity of these cells . It has recently been reported that rheumatoid arthritis synovial T lymphocytes express CD40L at a low level. These molecules can be dramatically upregulated when T cells are activated. In this context, stimulation of self-reactive T lymphocytes in the synosium will be induced through GM-CSF and TNF-α along with CD80+ C086+ DCs .
As mentioned above, cytokines can control the development and differentiation of DCs. For example, the combination of GM-CSF and TNF-α can promote differentiation of CD34+ blood stem cells into DCs in humans . Phenotypically these cells are CD4+CD11C+ since Langerhans DCs and other DC family numbers express CD4 molecules that can bind to the HIV surface envelope protein gp 120 . This makes a possibility stronger that DCs may contribute to HIV pathology. On one hand, in vivo and in vitro experiments indicate that the replication of HIV-1 virus occurs during cognate CD4+ T cell activation through DCs. On the other hand, there is evidence that the features of HIV pathology are an accumulation of HIV virus in the germinal centers, which is T cell rich and where a novel DC population has recently been identified . Both the APC function of DCs and their close interaction with CD4+ T cells suggests that germinal centers of lymph nodes may provide an additional site for HIV viral replication [42–44].
Moreover, DCs in transplanted organs are involved and they represent potent "passenger leukocytes" that sensitize host graft antigens and trigger rejection . Studies have shown that the depletion of DCs from mouse islets or thyroid tissue prolonged survival in allogeneic recipients . Other studies on the function of DCs after transplantation of skin and heart tissues to allogeneic recipients have shown that soon after grafting, DCs enter the recipient's lymphoid tissues . Thus, there appears to be a sensitization of host T cells which occurs primarily in these tissues when they encounter the graft-derived, allogeneic DCs. Austyn et al. showed recently that host DCs can also present graft antigens to host T cells . In this process it seems that host DCs bearing graft molecules would migrate into the secondary lymphoid organs to sensitize and activate T lymphocytes and induce graft rejection.
It is clear now, that cancer cells can express tumor associated antigens, which are recognized by host T cells. These T cells may not be able to reject tumor cells. These molecules, then, are not immunogenic. In order to become immunogenic they must be processed and presented by professional antigen presenting cells (APC). Since DCs possess relevant features, e.g. a) internalizing of immunogenic antigen through endocytosis, b) phagocytosis for subsequent processing and presentation of several antigens to T cells, and c) migration capability, they could acquire tumor antigen.
In the past few years the role of DCs in cancer has been suggested. There is evidence that DCs can induce immunity to tumors if they are administrated to animals or exposed to tumor associated antigen (TAA) before or when the tumor is inoculated into animals [47–49]. For example, Boczkowski et al.  conducted several elegant experiments to demonstrate that DCs pulsed with synthesized chicken ovalbumin (OVA) RNA were more effective than OVA peptide-pulsed DCs in activating primary OVA specific-CTL responses in vitro. This finding shows that the amplification of antigens from a small number of tumor cells is feasible, thus increasing the possibility of utilizing RNA-pulsed DC based vaccines for patients bearing very small tumors .
Studies demonstrate that when DCs are pulsed with tumor antigens in ex vivo, and these cells subsequently readministrated, specific immunity is established . In addition, several studies showed that tumor-specific CD8+ cytotoxic T lymphocytes (CTL) constitute an important effector arm of the anti-tumor immune response [52, 53]. In this context to elicit specific immunity against tumor cells, DCs were pulsed with protein or peptide in the presence of lipid  or transfected with DNA  were capable of eliciting primary CTL responses in vitro.
Although prior investigations have established that targeting immune cells to tumors may improve immunity [47–55], in the case of DCs, however, it has been shown [56–62] that the tumor microenvironment is detrimental to DC function, and in fact may condition DCs to induce a T cell response that anergizes or suppresses tumor-specific immunity . Thus, targeting DCs directly to tumors, as demonstrated by several studies, may be inefficient. Therefore, methods should be developed in order to target DCs by immunogenic TAAs outside the tumor microenvironment to improve immunity.