CD155 is involved in negative selection and is required to retain terminally maturing CD8 T cells in thymus.
During their final maturation in the medulla, semimature single-positive (SP) thymocytes downregulate activation markers and subsequently exit into the periphery. Although semimature CD4(+) SP cells are sensitive to negative selection, the timing of when negative selection occurs in the CD8 lineage remains elusive. We show that the abundance of terminally matured CD8(+) SP cells in adult thymus is modulated by the genetic background. Moreover, in BALB/c mice, the frequency of terminally matured CD8(+) SP cells, but not that of CD4(+) SP cells present in thymus, varies depending on age. In mice lacking expression of the adhesion receptor CD155, a selective deficiency of mature CD8(+) SP thymocytes was observed, emerging first in adolescent animals at the age when these cells start to accumulate in wild-type thymus. Evidence is provided that the mature cells emigrate prematurely when CD155 is absent, cutting short their retention time in the medulla. Moreover, in nonmanipulated wild-type mice, semimature CD8(+) SP thymocytes are subjected to negative selection, as reflected by the diverging TCR repertoires present on semimature and mature CD8(+) T cells. In CD155-deficient animals, a shift was found in the TCR repertoire displayed by the pool of CD8(+) SP cells, demonstrating that CD155 is involved in negative selection.
Qiu
Quan
Q
Institute of Immunology, Hannover Medical School, Hannover, Germany.
Ravens
Inga
I
Seth
Sebastian
S
Rathinasamy
Anchana
A
Maier
Michael K
MK
Davalos-Misslitz
Ana
A
Forster
Reinhold
R
Bernhardt
Günter
G
D000375:Aging / Q000235:genetics / Q000276:immunology; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D002465:Cell Movement / Q000235:genetics / Q000276:immunology*; D016922:Cellular Senescence / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D011991:Receptors, Virus / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism
D011991:Receptors, Virus; C066100:poliovirus receptor