The role of CD4⁺ T cells in tumor and chronic viral immune responses

Abstract

Immunotherapies are mainly aimed to promote a CD8+ T cell response rather than a CD4+ T cell response as cytotoxic T lymphocytes (CTLs) can directly kill target cells. Recently, CD4+ T cells have received more attention due to their diverse roles in tumors and chronic viral infections. In antitumor and antichronic viral responses, CD4+ T cells relay help signals through dendritic cells to indirectly regulate CD8+ T cell response, interact with B cells or macrophages to indirectly modulate humoral immunity or macrophage polarization, and inhibit tumor blood vessel formation. Additionally, CD4+ T cells can also exhibit direct cytotoxicity toward target cells. However, regulatory T cells exhibit immunosuppression and CD4+ T cells become exhausted, which promote tumor progression and chronic viral persistence. Finally, we also outline immunotherapies based on CD4+ T cells, including adoptive cell transfer, vaccines, and immune checkpoint blockade. Overall, this review summarizes diverse roles of CD4+ T cells in the antitumor or protumor and chronic viral responses, and also highlights the immunotherapies based on CD4+ T cells, giving a better understanding of their roles in tumors and chronic viral infections.

New Immunological Markers in Chromoblastomycosis—The Importance of PD-1 and PD-L1 Molecules in Human Infection

“…IL-4 is also related to the persistence of Candida albicans in macrophages in vitro [53] and the progression of aspergillosis in mice [54,55]; therefore, IL-4 may have contributed to the chronicity of CBM in the patients studied here. In addition to IL-4, the cytokine IL-10 inhibits the production of IFN-γ and reduces the expression of the major histocompatibility complex and co-stimulatory molecules [39]. Therefore, these data suggest that both cytokine-producing cells may inhibit the interaction between lymphocytes as phagocytic cells, allowing for the progression of CBM [50,56].…”

“…In this study, the lymphocytes present in the inflammatory infiltrate of the patients comprised the CD4 and CD8 subsets. Naive CD4 + T lymphocytes can be differentiated according to some stimuli into subsets, such as Th1, Th2, Th17, and regulatory T cells, which in turn produce mainly IFN-γ, IL-4, IL-17, and IL-10 cytokines, respectively [39]. In the present study, a high density of CD4 lymphocytes was detected in the inflammatory infiltrate of patients with CBM, which was correlated with high production of IFN-γ and IL-17, suggesting that both Th1 and Th17 immune responses were activated to eliminate parasitic forms of fungi.…”