Generation of CD4(+)CD45RA(+) effector T cells by stimulation in the presence of cyclic adenosine 5'-monophosphate-elevating agents.
After TCR cross-linking, naive CD4(+)CD45RA(+) T cells switch to the expression of the CD45RO isoform and acquire effector functions. In this study we have shown that cAMP-elevating agents added to anti-CD3- and anti-CD28-stimulated cultures of T lymphocytes prevent acquisition of the CD45RO(+) phenotype and lead to the generation of a new subpopulation of primed CD4(+)CD45RA(+) effector cells (cAMP-primed CD45RA). These cells displayed a low apoptotic index, as the presence of dibutyryl cAMP (dbcAMP)-rescued cells from CD3/CD28 induced apoptosis. Inhibition of CD45 splicing by dbcAMP was not reverted by addition of exogenous IL-2. cAMP-primed CD45RA cells had a phenotype characteristic of memory/effector T lymphocytes, as they showed an up-regulated expression of CD2, CD44, and CD11a molecules, while the levels of CD62L Ag were down-regulated. These cells also expressed the activation markers CD30, CD71, and HLA class II Ags at an even higher level than CD3/CD28-stimulated cells in the absence of dbcAMP. In agreement with this finding, cAMP-primed CD45RA cells were very efficient in triggering allogenic responses in a MLR. In addition, cAMP-primed CD45RA cells produce considerable amounts of the Th2 cytokines, IL-4, IL-10, and IL-13, whereas the production of IFN-gamma and TNF-alpha was nearly undetectable. The elevated production of IL-13 by neonatal and adult cAMP-primed CD45RA cells was specially noticeable. The cAMP-dependent inhibition of CD45 splicing was not caused by the production of immunosuppressor cytokines. These results suggest that within the pool of CD4(+)CD45RA(+) cells there is a subpopulation of effector lymphocytes generated by activation in the presence of cAMP-elevating agents.
Department of Functional Biology, Area of Immunology, Universidad de Oviedo, Spain.
Ana
A
Suárez
Lourdes
L
Mozo
Carmen
C
Gutiérrez
D000328:Adult; D000954:Antigens, Surface / Q000032:analysis; D003994:Bucladesine / Q000494:pharmacology; D018106:CD28 Antigens / Q000502:physiology; D015704:CD4 Antigens / Q000032:analysis*; D000242:Cyclic AMP / Q000502:physiology*; D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D016130:Immunophenotyping; D016753:Interleukin-10 / Q000502:physiology; D007376:Interleukin-2 / Q000502:physiology; D015847:Interleukin-4 / Q000502:physiology; D017493:Leukocyte Common Antigens / Q000032:analysis*; D016176:T-Lymphocyte Subsets / Q000502:physiology*
D000954:Antigens, Surface; D018106:CD28 Antigens; D015704:CD4 Antigens; D016207:Cytokines; D007376:Interleukin-2; D016753:Interleukin-10; D015847:Interleukin-4; D003994:Bucladesine; D000242:Cyclic AMP; D017493:Leukocyte Common Antigens