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Human CD4 + T lymphocytes with increased intracellular cAMP levels exert regulatory functions by releasing extracellular cAMP
Author(s) -
Vendetti Silvia,
Patrizio Mario,
Riccomi Antonella,
De Magistris Maria Teresa
Publication year - 2006
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0106072
Subject(s) - biology , extracellular , intracellular , microbiology and biotechnology , immunology
We have previously shown that cholera toxin (CT) and other cAMP‐elevating agents induce up‐regulation of the inhibitory molecule CTLA‐4 on human resting T lymphocytes. In this study, we evaluated the function of these cells. We found that purified human CD4 + T lymphocytes pretreated with CT were able to inhibit proliferation of autologous PBMC in a dose‐dependent manner. It is interesting that this phenomenon was not mediated by inhibitory cytokines such as IL‐10, IL‐4, or TGF‐β but was in part caused by the release of extracellular cAMP by the CD4 + T lymphocytes. Purified CD4 + T cells pretreated with forskolin, a transient cAMP inducer, or with dibutyryl cAMP, an analog of cAMP, did not exert suppressive functions, suggesting that a sustained production of cAMP, such as that induced by CT, was required to identify a novel regulatory function mediated by CD4 + T cells. Our results show that CD4 + T lymphocytes can exert regulatory functions through the release of extracellular cAMP and that the cyclic nucleotide acts as a primary messenger, which could play a biological role in the modulation of immune responses.