Asymmetric T lymphocyte division in the initiation of adaptive immune responses.
A hallmark of mammalian immunity is the heterogeneity of cell fate that exists among pathogen-experienced lymphocytes. We show that a dividing T lymphocyte initially responding to a microbe exhibits unequal partitioning of proteins that mediate signaling, cell fate specification, and asymmetric cell division. Asymmetric segregation of determinants appears to be coordinated by prolonged interaction between the T cell and its antigen-presenting cell before division. Additionally, the first two daughter T cells displayed phenotypic and functional indicators of being differentially fated toward effector and memory lineages. These results suggest a mechanism by which a single lymphocyte can apportion diverse cell fates necessary for adaptive immunity.
Chang
John T
JT
Abramson Family Cancer Research Institute and Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Palanivel
Vikram R
VR
Kinjyo
Ichiko
I
Schambach
Felix
F
Intlekofer
Andrew M
AM
Banerjee
Arnob
A
Longworth
Sarah A
SA
Vinup
Kristine E
KE
Mrass
Paul
P
Oliaro
Jane
J
Killeen
Nigel
N
Orange
Jordan S
JS
Russell
Sarah M
SM
Weninger
Wolfgang
W
Reiner
Steven L
SL
D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation; D015703:Antigens, CD / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D002454:Cell Differentiation; D002455:Cell Division; D019070:Cell Lineage; D016764:Cell Polarity; D003713:Dendritic Cells / Q000276:immunology; D007156:Immunologic Memory; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008089:Listeria monocytogenes / Q000276:immunology; D008088:Listeriosis / Q000276:immunology; D008213:Lymphocyte Activation; D008565:Membrane Proteins / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008938:Mitosis; D009419:Nerve Tissue Proteins / Q000032:analysis; D011493:Protein Kinase C / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D017471:Receptors, Interferon / Q000032:analysis; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D000096743:Interferon gamma Receptor; D000099221:Protein Kinase C zeta
D015703:Antigens, CD; D016827:CD8 Antigens; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011493:Protein Kinase C; D011948:Receptors, Antigen, T-Cell; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor; D000099221:Protein Kinase C zeta; C106293:Numb protein, mouse; C508433:scrib protein, mouse