Abstract
Lymph nodes (LNs) are central in the generation of adaptive immune responses. Follicular helper CD4 T (Tfh) cells, a highly differentiated CD4 population, provide critical help for the development of antigen-specific B cell responses within the germinal center. Throughout the past decade, numerous studies have revealed the important role of Tfh cells in Human Immunodeficiency Virus (HIV) pathogenesis as well as in the development of neutralizing antibodies post-infection and post-vaccination. It has also been established that tumors influence various immune cell subsets not only in their proximity, but also in draining lymph nodes. The role of local or tumor associated lymph node Tfh cells in disease progression is emerging. Comparative studies of Tfh cells in chronic infections and cancer could therefore provide novel information with regards to their differentiation plasticity and to the mechanisms regulating their development.
Highlights
Given the important role the lymphatic system has in combating foreign pathogens, changes in Lymph Node (LN) architecture/cellularity have been recognized in a variety of infectious diseases
Understanding the follicular/germinal center (GC)- and T follicular helper (Tfh) cellimmune dynamics in Human Immunodeficiency Virus (HIV)/Simian Immunodeficiency Virus (SIV) infection is of great importance for (i) the identification of molecules/pathways associated with the development of broadly neutralizing antibodies that could inform the design of novel vaccine strategies targeting relevant GC cell populations and (ii) understanding the establishment and maintenance of a major viral reservoir [5], even in combination antiretroviral therapy (cART) treated donors [155]
Is this profile of chronically in vivo stimulated Tfh cells unique for HIV/SIV or there is a core, preserved molecular signature during Tfh cell development under different stimuli like cancer neoantigens? Does the etiology/type of cancer have an impact on this profile? Relevant studies will provide critical information about the plasticity of the Tfh cell differentiation program
Summary
Given the important role the lymphatic system has in combating foreign pathogens, changes in Lymph Node (LN) architecture/cellularity have been recognized in a variety of infectious diseases. Though, that different follicular CD4 T cell subsets are presumably exposed to different local signals within the follicle Delineation of these signals, as well as the connection between phenotype and function of Tfh cell subsets, is an important step toward the comprehensive understanding of Tfh cell biology and their role in human diseases. Tfr cells can suppress GC reactivity [43] either by altering such mutual regulation- a process mediated in part by CTLA-4 [49]- or by directly affecting B or Tfh cells [43, 50] They represent a small minority of follicular CD4 T cells, the presence of Tfr cells aids in limiting the GC response to prevent uncontrolled B cell proliferation and the consequences thereof, such as the production of antibodies that recognize “self ” antigens [37, 44]
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