Cutting edge: two distinct mechanisms lead to impaired T cell homeostasis in Janus kinase 3- and CTLA-4-deficient mice
Gozalo, Sara ; McNally, James M. ; Lin, Meei-Yun ; Chambers, Cynthia A. ; Berg, Leslie J.
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UMass Chan Affiliations
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Keywords
Antigens, CD
Antigens, Differentiation
Cell Differentiation
Clone Cells
Homeostasis
*Immunoconjugates
Janus Kinase 3
Lymphocyte Activation
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Protein-Tyrosine Kinases
Receptors, Antigen, T-Cell, alpha-beta
T-Lymphocytes
Life Sciences
Medicine and Health Sciences
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Abstract
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.
Source
J Immunol. 2001 Jan 15;166(2):727-30.