Spontaneous and homeostatic proliferation of CD4 T cells are regulated by different mechanisms.
Transfer of naive CD4 T cells into lymphopenic mice initiates a proliferative response of the transferred cells, often referred to as homeostatic proliferation. Careful analysis reveals that some of the transferred cells proliferate rapidly and undergo robust differentiation to memory cells, a process we have designated spontaneous proliferation, and other cells proliferate relatively slowly and show more limited evidence of differentiation. In this study we report that spontaneous proliferation is IL-7 independent, whereas the slow proliferation (referred to as homeostatic proliferation) is IL-7 dependent. Administration of IL-7 induces homeostatic proliferation of naive CD4 T cells even within wild-type recipients. Moreover, the activation/differentiation pattern of the two responses are clearly distinguishable, indicating that different activation mechanisms may be involved. Our results reveal the complexity and heterogeneity of lymphopenia-driven T cell proliferation and suggest that they may have fundamentally distinct roles in the maintenance of CD4 T cell homeostasis.
Min
Booki
B
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. minb@ccf.org
Yamane
Hidehiro
H
Hu-Li
Jane
J
Paul
William E
WE
D019264:Adoptive Transfer / Q000379:methods; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000473:pathology / Q000637:transplantation; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics; D006706:Homeostasis / Q000235:genetics / Q000276:immunology*; D015918:Infusion Pumps, Implantable; D015851:Interleukin-7 / Q000008:administration & dosage / Q000502:physiology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology / Q000473:pathology; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D011994:Recombinant Proteins / Q000008:administration & dosage
D004268:DNA-Binding Proteins; D015851:Interleukin-7; C499308:Rag2 protein, mouse; D011948:Receptors, Antigen, T-Cell; D011994:Recombinant Proteins; C064655:V(D)J recombination activating protein 2