Cutting edge: two distinct mechanisms lead to impaired T cell homeostasis in Janus kinase 3- and CTLA-4-deficient mice.
Cytokine receptor signaling and costimulatory receptor signaling play distinct roles in T cell activation. Nonetheless, deficiencies in either of these pathways lead to seemingly similar phenotypes of impaired T cell homeostasis. A dramatic expansion of CD4(+) peripheral T cells with an activated phenotype has been observed in both Janus kinase (Jak) 3-deficient and CTLA-4-deficient mice. Despite these similarities, the mechanisms driving T cell expansion may be distinct. To address this possibility, we examined the TCR repertoire of peripheral T cells in Jak3(-/-) and CTLA-4(-/-) mice using complementarity-determining region 3 spectratype analysis. Interestingly, a restricted and highly biased TCR repertoire was observed in the Jak3(-/-) T cells, strongly supporting a role for foreign Ag in the activation and expansion of these cells. In contrast, CTLA-4(-/-) T cells had a diverse and unbiased TCR repertoire, suggestive of a universal, Ag-independent mechanism of activation and expansion. These findings provide insight into the diverse mechanisms controlling T cell homeostasis.
Gozalo-Sanmillan
S
S
Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
McNally
J M
JM
Lin
M Y
MY
Chambers
C A
CA
Berg
L J
LJ
D000069594:Abatacept; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D060908:CTLA-4 Antigen; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002999:Clone Cells; D006706:Homeostasis / Q000235:genetics* / Q000276:immunology*; D018796:Immunoconjugates; D053616:Janus Kinase 3; D008213:Lymphocyte Activation / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011505:Protein-Tyrosine Kinases / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D018796:Immunoconjugates; D016693:Receptors, Antigen, T-Cell, alpha-beta; D000069594:Abatacept; D011505:Protein-Tyrosine Kinases; C507935:Jak3 protein, mouse; D053616:Janus Kinase 3