Cholera Caused by Vibrio cholerae O1 Induces T-Cell Responses in the Circulation

Considerable effort is being made to understand the acute and memory antibody responses in natural cholera infection, while rather less is known about the roles of cellular immune responses involving T and B lymphocytes. We studied responses in adult patients hospitalized with cholera caused by Vibrio cholerae O1. Peripheral blood mononuclear cells from patients (n = 15) were analyzed by flow cytometry after stimulation with V. cholerae O1 membrane protein (MP) or toxin-coregulated pilus antigen (TcpA). The gamma interferon (IFN-γ) and interleukin-13 (IL-13) responses in stimulated-lymphocyte supernatants were studied. The responses were compared with those of healthy controls (n = 10). Patients responded with increased frequencies of gut-homing CD4⁺ T cells (CD4⁺ β7⁺), gut-homing CD8⁺ T cells (CD8⁺ β7⁺), and gut-homing B cells (CD19⁺ β7⁺) at the early and/or late convalescent stages compared to the acute stage. After stimulation with MP or TcpA, proliferation of CD4⁺ and CD8⁺ T cells was increased at the acute stage and/or early convalescent stage compared to healthy controls. Increased IL-13 and IFN-γ responses were observed after antigenic stimulation at the acute and convalescent stages compared to healthy controls. Thus, increases in the levels of gut-homing T and B cells, as well as involvement of CD8 and CD4 Th1-mediated (IFN-γ) and CD4 Th2-mediated (IL-13) cytokine responses, take place in acute dehydrating disease caused by V. cholerae O1. Further studies are needed to determine if such responses are also stimulated after immunization with oral cholera vaccines and if these responses play a role in protection following exposure to cholera.Vibrio cholerae O1 is a common causative agent of acute watery diarrhea in children and adults in the developing world (1, 3, 10, 19). After colonizing the proximal small intestine, this bacterium produces cholera toxin, which induces a profuse secretory diarrhea. Cholera remains a key public health problem that results in epidemics in resource-poor settings.It is believed that the immune response to cholera is initiated by antigen presentation in the Peyer''s patches of the gastrointestinal mucosa, followed by migration of the stimulated antigen-specific B cells to regional lymph nodes and differentiation of these cells into specific antibody-secreting cells (28). Stimulation of the common mucosal immune system leads to production of both local and systemic antibodies (2, 15, 27) to virulence antigens of V. cholerae (25, 28).Natural cholera infection is believed to give rise to long-term protection against subsequent disease. Robust systemic and mucosal antibodies are produced to the V. cholerae lipopolysaccharide, to cholera toxin, and to colonization factors, including the major subunit of the toxin-coregulated pilus, TcpA (2, 24, 25, 28). We have recently shown that there is induction of memory B-cell responses following infection, which may play a role in longer-lasting protection (14). In addition, recent evidence suggests that an innate component of the immune system may also play a role in the host response to cholera (9, 22, 26). Studies with experimental animals have shown that the mucosal immune response to cholera toxin is T cell dependent and that CD4 T helper cells have an important role (7, 12, 13). However, not much is known about the role of the adaptive cellular immune responses in patients with cholera. The aim of the present study was to decipher the role of T- and B-cell-mediated immune responses in natural cholera infection in adults hospitalized with dehydrating illness, who were followed from the acute stage to convalescence.