Is a Human CD8 T-Cell Vaccine Possible, and if So, What Would It Take? CD8 T-Cell-Mediated Protective Immunity and Vaccination against Enteric Bacteria

Abstract

Although induction of CD8⁺ responses is widely accepted as critical in clearing viral infections and necessary for effective vaccines against viruses, much less is known regarding the role of these cells in bacterial and other infections, particularly those that enter the host via the gastrointestinal tract. In this commentary, I discuss the likelihood that CD8⁺ responses are also important in protection from intestinal Gram-negative bacteria, as well as the many factors that should be taken into consideration during the development of vaccines, based on eliciting long-term protection predominantly mediated by CD8⁺ responses against these organisms.

Figure 1.

In vitro stimulation of peripheral blood mononuclear cells (PBMCs) isolated from wild-type (WT) S. Typhi–exposed participants with S. Typhi–infected targets and ex vivo studies: Experimental design. PBMCs obtained before and at various times after oral exposure to the WT S. Typhi Quailes strain were incubated in vitro with autologous Epstein–Barr virus transformed lymphoblastoid B-cell lines (EBV-LCL), 721.221.AEH EBV-LCL (to measure HLA-E-restricted responses) or blasts infected with WT Salmonella enterica serovar Typhi (S. Typhi). After an overnight incubation, cells were fixed and stained for flow cytometry (14-color) or mass cytometry (up to 34 metal-conjugated monoclonal antibodies) depending on whether CD4⁺ or CD8⁺ T effector and/or memory subsets (T_EM), or regulatory (Tregs) T cells were evaluated. Activation and other characteristics of B cells, antigen-presenting cells (APCs), mucosal-associated invariant T cells (MAITs), or other populations were evaluated ex vivo without stimulation. IFN-γ, Interferon γ; TNF-α, tumor necrosis factor α, MIP-1β, macrophage inflammatory protein-1β, IL-17A, interleukin 17A; FoxP3, forkhead box P3; CTLA-4, cytotoxic T-lymphocyte-associated antigen 4; LFA-1/CD11a, lymphocyte function-associated antigen-1; CD279/PD1, programmed cell death-1; CCR6, C-C chemokine receptor type 6; CCR7, C-C chemokine receptor type 7.