title: Homeostatic division is not necessary for antigen-specific CD4+ memory T cell persistence.
abstract: CD4(+) memory T cells are generated in response to infection or vaccination, provide protection to the host against reinfection, and persist through a combination of enhanced survival and slow homeostatic turnover. We used timed deletion of the TCR-signaling adaptor molecule Src homology 2 domain-containing phosphoprotein of 76 kDa (SLP-76) with MHC:peptide tetramers to study the requirements for tonic TCR signals in the maintenance of polyclonal Ag-specific CD4(+) memory T cells. SLP-76-deficient I-A(b):gp61 cells are unable to rapidly generate effector cytokines or proliferate in response to secondary infection. In mice infected with lymphocytic choriomeningitis virus (LCMV) or Listeria monocytogenes expressing the LCMV gp61-80 peptide, SLP-76-deficient I-A(b):gp61(+) cells exhibit reduced division, similar to that seen in in vitro-generated CD44(hi) and endogenous CD4(+)CD44(hi) cells. Competitive bone marrow chimera experiments demonstrated that the decrease in homeostatic turnover in the absence of SLP-76 is a cell-intrinsic process. Surprisingly, despite the reduction in turnover, I-A(b):gp61(+) Ag-specific memory cells persist in normal numbers for >30 wk after LCMV infection in the absence of SLP-76. These data suggest the independent maintenance of a population of Ag-specific CD4(+) memory T cells in the absence of SLP-76 and normal levels of homeostatic division.
authors.affiliation: Immunology Graduate Group, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Evann
authors.initials: E
authors.lastname: Corbo-Rodgers
authors.forename: Karla R
authors.initials: KR
authors.lastname: Wiehagen
authors.forename: Elizabeth S
authors.initials: ES
authors.lastname: Staub
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Maltzman
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000276:immunology; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D002455:Cell Division / Q000235:genetics / Q000276:immunology*; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology* / Q000378:metabolism; D006706:Homeostasis / Q000235:genetics / Q000276:immunology*; D007156:Immunologic Memory / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010750:Phosphoproteins / Q000235:genetics / Q000276:immunology; D011828:Radiation Chimera / Q000276:immunology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018984:Epitopes, T-Lymphocyte; D010750:Phosphoproteins; C092947:SLP-76 signal Transducing adaptor proteins