CD4 T cells in protection from influenza virus: Viral antigen specificity and functional potential

Abstract

CD4 T cells convey a number of discrete functions to protective immunity to influenza, a complexity that distinguishes this arm of adaptive immunity from B cells and CD8 T cells. Although the most well recognized function of CD4 T cells is provision of help for antibody production, CD4 T cells are important in many aspects of protective immunity. Our studies have revealed that viral antigen specificity is a key determinant of CD4 T cell function, as illustrated both by mouse models of infection and human vaccine responses, a factor whose importance is due at least in part to events in viral antigen handling. We discuss research that has provided insight into the diverse viral epitope specificity of CD4 T cells elicited after infection, how this primary response is modified as CD4 T cells home to the lung, establish memory, and after challenge with a secondary and distinct influenza virus strain. Our studies in human subjects point out the challenges facing vaccine efforts to facilitate responses to novel and avian strains of influenza, as well as strategies that enhance the ability of CD4 T cells to promote protective antibody responses to both seasonal and potentially pandemic strains of influenza.

Fumaric acid ester‐induced T‐cell lymphopenia in the real‐life treatment of psoriasis

“…39,68 However, CD4 + T cells induce B-cell differentiation in antibody-secreting plasma cells, monocyte and macrophage phagocytic capabilities, and CD8 + T-cell cytotoxic function. 39,69,70 Comparable with these and our earlier results, 24,59 Spencer et al 58 found a significant CD19 + B-cell count reduction by 37.5% after 12 months of DMF treatment. Longbrake et al 68 recently reported that DMF induces a phenotypic shift among circulating B cells, reducing the proportion of memory B cells and expanding the proportion of na€ ıve B cells.…”

With a Little Help from T Follicular Helper Friends: Humoral Immunity to Influenza Vaccination

“…The antigenic specificity of CD4 + T cells, which includes the Tfh cell population, is an important parameter that needs to be considered in the design of protective vaccines, as it can affect both the breadth and functionality of the CD4 + T cell responses (42,43). Following IIV immunization, the specificity of activated cTfh cells against influenza Ag has been confirmed by stimulation with heat-killed IAV or IIV or influenza-derived peptide pools and measuring cytokine (IL-21, IL-2, IFN-g) production and/or upregulation of the T helper activation marker CD40L (also referred to as CD154) or activation markers (CD200, CD69) (17,22,31).…”

CD4+T follicular helper (Tfh) cells in human tonsil and blood are clonally convergent, but divergent from non-Tfh CD4+cells

“…To compare the repertoire of antigen-specific Tfh and non-Tfh cells in peripheral blood and their representation in tonsil populations, responses to the haemagglutinin (HA) protein H3 from influenza virus A/Wisconsin/67/2005 were studied (Alam and Sant, 2011;Fazilleau et al, 2007;Sant et al, 2018). To assess the relative abundance of memory CD4 + T cells reactive with HA protein the T cell library method (Geiger et al, 2009) was used to determine the precursor frequency of HA-reactive cells in isolated memory CD4 + T cell populations and to characterize the cTfh and cNon-Tfh CD4 + memory repertoire in 3 healthy donors ( Figure 6A).…”

“…TCR repertoire analyses revealed considerable overlap between peripheral and tonsillar Tfh cells, and a complete disparity between Tfh cells and CXCR5memory CD4 + T cells. In addition, memory Tfh and non-Tfh cells from blood reactive with the haemagglutinin (HA) protein from influenza virus, one of the most frequent seasonal infections, were studied (Alam and Sant, 2011;Fazilleau et al, 2007;Sant et al, 2018). HA-specific CD4 + memory T cells were enriched in CXCR3 + cTfh cells and HA-specific cTfh cell clones could be found in the tonsillar CXCR3 + Tfh population.…”