[HTML][HTML] Multifunctional TH1 cells define a correlate of vaccine-mediated protection against Leishmania major

PA Darrah, DT Patel, PM De Luca, RWB Lindsay… - Nature medicine, 2007 - nature.com
PA Darrah, DT Patel, PM De Luca, RWB Lindsay, DF Davey, BJ Flynn, ST Hoff, P Andersen
Nature medicine, 2007nature.com
CD4+ T cells have a crucial role in mediating protection against a variety of pathogens
through production of specific cytokines. However, substantial heterogeneity in CD4+ T-cell
cytokine responses has limited the ability to define an immune correlate of protection after
vaccination. Here, using multiparameter flow cytometry to assess the immune responses
after immunization, we show that the degree of protection against Leishmania major
infection in mice is predicted by the frequency of CD4+ T cells simultaneously producing …
Abstract
CD4+ T cells have a crucial role in mediating protection against a variety of pathogens through production of specific cytokines. However, substantial heterogeneity in CD4+ T-cell cytokine responses has limited the ability to define an immune correlate of protection after vaccination. Here, using multiparameter flow cytometry to assess the immune responses after immunization, we show that the degree of protection against Leishmania major infection in mice is predicted by the frequency of CD4+ T cells simultaneously producing interferon-γ, interleukin-2 and tumor necrosis factor. Notably, multifunctional effector cells generated by all vaccines tested are unique in their capacity to produce high amounts of interferon-γ. These data show that the quality of a CD4+ T-cell cytokine response can be a crucial determinant in whether a vaccine is protective, and may provide a new and useful prospective immune correlate of protection for vaccines based on T-helper type 1 (TH1) cells.
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