title: Regulation of CD4+ T-cell contraction during pathogen challenge.
abstract: Signals orchestrating productive CD4+ T-cell responses are well documented; however, the regulation of contraction of CD4+ T-cell effector populations following the resolution of primary immune responses is not well understood. While distinct mechanisms of T-cell death have been defined, the relative importance of discrete death pathways during the termination of immune responses in vivo remains unclear. Here, we review the current understanding of cell-intrinsic and -extrinsic variables that regulate contraction of CD4+ T-cell effector populations through multiple pathways that operate both initially during T-cell priming and later during the effector phase. We discuss the relative importance of antigen-dependent and -independent mechanisms of CD4+ T-cell contraction during in vivo responses, with a special emphasis on influenza virus infection. In this model, we highlight the roles of greater differentiation and presence in the lung of CD4+ effector T cells, as well as their polarization to particular T-helper subsets, in maximizing contraction. We also discuss the role of autocrine interleukin-2 in limiting the extent of contraction, and we point out that these same factors regulate contraction during secondary CD4+ T-cell responses.
authors.affiliation: Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
authors.forename: K Kai
authors.initials: KK
authors.lastname: McKinstry
authors.forename: Tara M
authors.initials: TM
authors.lastname: Strutt
authors.forename: Susan L
authors.initials: SL
authors.lastname: Swain
mesh_terms: D017209:Apoptosis / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007251:Influenza, Human / Q000276:immunology* / Q000821:virology; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D018448:Models, Immunological; D015398:Signal Transduction / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism
chemical_list: D007376:Interleukin-2