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Promiscuous Foxp3‐cre activity reveals a differential requirement for CD28 in Foxp3 + and Foxp3 − T cells
Author(s) -
Franckaert Dean,
Dooley James,
Roos Evelyne,
Floess Stefan,
Huehn Jochen,
Luche Herve,
Fehling Hans Joerg,
Liston Adrian,
Linterman Michelle A,
Schlenner Susan M
Publication year - 2015
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1038/icb.2014.108
Subject(s) - foxp3 , cd28 , allele , biology , immunology , genetics , t cell , immune system , gene
Costimulatory signals by CD28 are critical for thymic regulatory T‐cell (Treg) development. To determine the functional relevance of CD28 for peripheral Treg post thymic selection, we crossed the widely used Forkhead box protein 3 (Foxp3)‐CreYFP mice to mice bearing a conditional Cd28 allele. Treg‐specific CD28 deficiency provoked a severe autoimmune syndrome as a result of a strong disadvantage in competitive fitness and proliferation of CD28‐deficient Tregs. By contrast, Treg survival and lineage integrity were not affected by the lack of CD28. This data demonstrate that, even after the initial induction requirement, Treg maintain a higher dependency on CD28 signalling than conventional T cells for homeostasis. In addition, we found the Foxp3‐CreYFP allele to be a hypomorph, with reduced Foxp3 protein levels. Furthermore, we report here the stochastic activity of the Foxp3‐CreYFP allele in non‐Tregs, sufficient to recombine some conditional alleles (including Cd28 ) but not others (including R26‐RFP ). This hypomorphism and ‘leaky’ expression of the Foxp3‐CreYFP allele should be considered when analysing the conditionally mutated Treg.