Faculty Opinions recommendation of CD4+ T cells are required for the maintenance, not programming, of memory CD8+ T cells after acute infection.
Year: 2004
Type: peer-review
Abstract: Immunization in the absence of CD4 + T cell help results in defective CD8 + T cell memory, deficient recall responses and diminished protective immunity.Here we investigated at what stage during the immune response to pathogen CD4 + T cells are essential in the promotion of functional CD8 + T cell memory.Memory CD8 + T cell numbers decreased gradually in the absence of CD4 + T cells despite the presence of similar numbers of memory cell precursors at the peak of the effector phase.Adoptive transfer of effector or memory CD8 + T cells into wild-type or CD4 + T cell-deficient mice demonstrated that the presence of CD4 + T cells was important only after, not during, the early CD8 + T cell programming phase.In the absence of CD4 + T cells, memory CD8 + T cells became functionally impaired and decreased in quantity over time.We conclude that in the context of an acute infection, CD4 + T cells are required only during the maintenance phase of long-lived memory CD8 + T cells.The rapid and more efficacious response of memory T cells after the second encounter with a pathogen constitutes a hallmark trait of adaptive immunity.The 'canonical' CD8 + T cell response to an acute infection consists of three well defined phases: the proliferation of naive cells to produce large numbers of effector cells; the contraction of these effector populations into memory cells once antigen is cleared; and the long-term maintenance of these memory cells.A brief encounter with antigen, as short as 24 h, can initiate 'programmed differentiation' in activated CD8 + T cells that leads to many rounds of antigen-independent division and the acquisition of effector function [1][2][3][4] .Effector cell populations at the peak of a CD8 response are also programmed to contract during their priming 5 .Thus, during an immune response to infection, intrinsic and external signals 'dictate' or program the complete CD8 + T cell response 6,7 .Although CD4 + T cells are not required for primary CD8 + T cell responses against pathogens, memory CD8 + T cell numbers and secondary responses to bacterial or viral challenge are decreased over time in a CD4 + T cell-deficient animal [8][9][10][11] .In those studies [8][9][10][11] , it was not apparent when the CD4 + T cell help was required to enhance the survival of the antigen-specific memory CD8 + T cells.It has been speculated that CD4 + T cells interacting with antigenpresenting cells also engage in crosstalk with CD8 + T cells during the proliferation or programming phase, delivering the necessary 'instructive' and/or survival signals for the generation of a fully functional memory CD8 + T cell pool [12][13][14] .It has also been suggested that
Author: Nicholas Restifo
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W4205805739