CD4 T cells in HIV: A Friend or Foe?

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Background

CD4 T cell responses constitute an important component of adaptive immunity and are critical regulators of vaccine-mediated protection. Their main function is to provide “help” to other cells, such as B cells, to support antibody production, affinity maturation and selection. CD8 T cells also play a role in memory development and the enhancement of cytotoxic functions. However, in the last decade our knowledge on CD4 T-cells, their diversity and function, has grown beyond the simplistic function of providing help. The family of CD4 T cells is now known to consist of highly specialized subsets such as T-regulatory cells, cytotoxic, Th17 cells, T follicular helper cells and tissue resident cells, among many others. All subsets can be defined by specific surface or intracellular markers, transcription factors and cytokine secretion profiles. Many questions remain with regard to plasticity between these subsets and their specific role in imparting vaccine mediated protection and modulating susceptibility to HIV infections.

HIV vaccine efforts embody strategies to enhance immune responses with a goal to achieve long lasting and ideally, sterilizing immunity. Antibodies (ideally broadly neutralizing) and cytotoxic T-cells should be present at the site of viral entry to stop infection and virus dissemination and CD4 T cells are needed to mount a robust vaccine response. However, in HIV infection, the induction of strong CD4 T-cell responses is a double-edged sword. This is because CD4 T cells also serve as primary targets of HIV. Activated CD4 T cells can be preferentially infected during the early stages of infection and high frequencies of vaccine-elicited CD4 T cells may limit vaccine-mediated protection. Moreover, specific lineages of CD4 T cells acting as HIV reservoirs have been reported in chronic HIV infections. More evidence is accumulating that some form of vaccine-specific CD4 T cell responses may increase susceptibility to HIV. Thus, given the paradoxical role of CD4 T cells, understanding the interplay between vaccine induced CD4 T cells and vaccine mediated protection is of paramount importance. In order to tip the balance in our favor, we require a rational design/delivery of vaccines in combination with newer immunotherapeutic strategies like engineered T-cells (CAR/TCR T-cells, armored T-cells) and CRISPR/CAS technologies.

This Research Topic is expected to bring together the current knowledge on CD4 T cells as important central mediators of adaptive immunity, while at the same time being the cellular target for multiplication and persistence of HIV.

We welcome Original Research, Method, Review, Clinical Trial and Perspective articles addressing, but not limited to, the following sub topics:

• Phenotypic and functional characterization of CD4 T cell lineages at the portal of entry and its association with acquisition of infection
• Role of immune mediators that might enhance or suppress CD4 T-cell susceptibility to HIV infection
• Interplay between immune system and local tissue microenvironment modulating the CD4 tissue residency and HIV susceptibility/resistance
• Role of CD4 T cells in eliciting mucosal antibody responses and cytotoxic effectors
• Role of non-immune mediators modulating HIV susceptibility / latency and HIV reservoir status of CD4 T cells
• Characterization of immune, microbial and metabolic genes signatures at mucosal surfaces and its association with enhanced or diminished protection of CD4 T cells
• Novel outside the box vaccine or therapeutic approaches to protect CD4 T cells and eliminate HIV

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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