Impact of Chronic Viral Infection on T-Cell Dependent Humoral Immune Response

Abstract

During the last decades, considerable efforts have been done to decipher mechanisms supported by microorganisms or viruses involved in the development, differentiation, and function of immune cells. Pathogens and their associated secretome as well as the continuous inflammation observed in chronic infection are shaping both innate and adaptive immunity. Secondary lymphoid organs are functional structures ensuring the mounting of adaptive immune response against microorganisms and viruses. Inside these organs, germinal centers (GCs) are the specialized sites where mature B-cell differentiation occurs leading to the release of high-affinity immunoglobulin (Ig)-secreting cells. Different steps are critical to complete B-cell differentiation process, including proliferation, somatic hypermutations in Ig variable genes, affinity-based selection, and class switch recombination. All these steps require intense interactions with cognate CD4+ helper T cells belonging to follicular helper lineage. Interestingly, pathogens can disturb this subtle machinery affecting the classical adaptive immune response. In this review, we describe how viruses could act directly on GC B cells, either through B-cell infection or by their contribution to B-cell cancer development and maintenance. In addition, we depict the indirect impact of viruses on B-cell response through infection of GC T cells and stromal cells, leading to immune response modulation.

TLR2 Stimulation Strengthens Intrahepatic Myeloid-Derived Cell-Mediated T Cell Tolerance through Inducing Kupffer Cell Expansion and IL-10 Production

“…The effect of iMDCs on CD4 + T cell activation is not addressed in this study because of the complexity of CD4 T cell differentiation. Naive CD4 + T cells give rise to many Th cell subsets such as Th1, Th2, Th17, Tregs, T follicular helper cells, and cytotoxic CD4 T cells upon TCR activation in a particular cytokine milieu (34)(35)(36). Different combinations of cytokines are required for the differentiation of different CD4 + T cell lineages; for example, IL-12 and IFN-g are for Th1; IL-4 and IL-2/IL-7/TSLP are for Th2; TGF-b and IL-6/IL-21/IL-23 are for Th17; and TGF-b and IL-10 are for Treg (34).…”

Free Light Chains as a Novel Diagnostic Biomarker of Immune System Abnormalities in Multiple Sclerosis and HIV Infection

“…The progressive weakening of the immune system may predispose HIV-infected patients to dementia, cardiovascular disease, and bone, liver and renal disorders. However, indisputably, it is well known that HIV infection is also, a risk factor for several B-cell and non-AIDS malignances, including Hodgkin and non-Hodgkin lymphoma [36, 37, 46, 47]. It should also be pointed out that HIV-associated lymphoma compared to lymphoma in HIV-negative patients is characterized by advanced diseases occurring more often, extranodal involvement, and being usually associated with Epstein-Barr virus [16].…”

Reconstitution of T follicular helper-humoral immune axis with elimination of hepatitis C virus

“…Chronic infection leads to prompt exhaustion of CD4 T cells 4 characterized by an increased programmed death-1 (PD-1), cytotoxic T-lymphocyte associated protein 4 (CTLA-4) expression and reduced effector cytokines including IL-21, IFN-γ and TNF-α [5][6][7] . Lower T follicular helper (T FH ) cell frequency and functionality is associated with impaired humoral response and uncontrolled virus replication, suggesting crucial involvement of T FH cells in governing viral infection 8 . During chronic HCV infection, decreased frequency of circulating IL-21 producing T FH cells has been reported 9 .…”