Predicting CD62L expression during the CD8+ T-cell response in vivo.
Acute infection leads to CD8(+) T-cell activation, division and differentiation. Following clearance of infection, cells revert to two distinct subsets of memory, central (T(CM)) and effector (T(EM)) memory. Adoptive transfer of naive T-cell receptor transgenic (TCR-tg) T cells has been used to study the differentiation of these memory subsets, which are often discriminated by expression of CD62L. Naive CD8(+) T cells are CD62L(high), and CD62L expression is lost during the 'effector' phase. Adoptive transfer studies show that higher transfer frequencies result in diminished T-cell expansion and a higher proportion CD62L(high). This suggests a relationship between CD62L expression and cell division, where division leads to conversion from CD62L(high) to CD62L(low) phenotype. To address this hypothesis we adoptively transferred graded numbers of OT-1 TCR-tg T cells from naive donors and tracked the kinetics and phenotype of the immune response after infection. We developed a simple mathematical model of division-linked CD62L differentiation, which we compared with the experimental data. Our results show that division-linked differentiation predicts the differences in proportion of cells CD62L(high) observed between responses of different adoptive transfer number and within individual mice. We calculate that approximately 20% of CD62L(high) cells convert to CD62L(low) during each division.
Complex Systems in Biology Group, Centre for Vascular Research, University of New South Wales, Kensington, New South Wales, Australia.
Timothy E
TE
Schlub
Vladimir P
VP
Badovinac
Jaime T
JT
Sabel
John T
JT
Harty
Miles P
MP
Davenport
D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D002452:Cell Count; D002454:Cell Differentiation; D002455:Cell Division; D007156:Immunologic Memory; D053699:Interleukin-7 Receptor alpha Subunit / Q000378:metabolism; D007700:Kinetics; D019041:L-Selectin / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D013154:Spleen / Q000166:cytology / Q000276:immunology
D053699:Interleukin-7 Receptor alpha Subunit; D019041:L-Selectin