Cell cycle progression following naive T cell activation is independent of Jak3/common gamma-chain cytokine signals.
T cell proliferation following activation is an essential aspect of the adaptive immune response. Multiple factors, such as TCR signaling, costimulation, and signals from cytokines, each contribute to determine the magnitude of T cell expansion. In this report, we examine in detail the role of Jak3/common gamma-chain-dependent cytokines in promoting cell cycle progression and proliferation of naive T cells. Using naive CD4+ T cells from Jak3-deficient mice and wild-type CD4+ T cells treated with a small molecule inhibitor of Jak3, we find that these cytokine signals are not required for proliferation; instead, they are important for the survival of activated T cells. In addition, we show that the percentage of cells entering the cell cycle and the percentage of cells in each round of cell division are comparable between Jak3-deficent and wild-type T cells. Furthermore, cell cycle progression and the regulated expression of key cell cycle proteins are independent of Jak3/common gamma-chain cytokine signals. These findings hold true over a wide range of TCR signal strengths. However, when CD28 costimulatory signals, but not TCR signals, are limiting, Jak3-dependent cytokine signals become necessary for the proliferation of naive T cells. Because CD28 signaling has been found to be dispensable for autoreactive T cell responses, these data suggest the potential for interfering with autoimmune T cell responses by inhibition of Jak3 signaling.
Shi
Min
M
Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
Lin
Tsung H
TH
Appell
Kenneth C
KC
Berg
Leslie J
LJ
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D002453:Cell Cycle / Q000235:genetics / Q000276:immunology*; D049109:Cell Proliferation / Q000187:drug effects; D053631:Interleukin Receptor Common gamma Subunit / Q000502:physiology*; D053616:Janus Kinase 3 / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D016192:Resting Phase, Cell Cycle / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000276:immunology*
D053631:Interleukin Receptor Common gamma Subunit; D047428:Protein Kinase Inhibitors; C507935:Jak3 protein, mouse; D053616:Janus Kinase 3