IL-7-dependent extrathymic expansion of CD45RA+ T cells enables preservation of a naive repertoire.
We have investigated the regulation of adult and cord blood CD45RA+ T cell proliferation and apoptosis to identify factors that may control the naive T cell pool. Cord CD45RA+ T cells were highly susceptible to spontaneous apoptosis as compared with CD45RA+ T cells from adults. Apoptosis was prevented by the addition of IL-2, IL-4, IL-7, and IL-15 which signal via the gamma-chain of the IL-2 receptor. IL-7 prevented the decrease in Bcl-2 and Bcl-xL and induced cell cycling in up to 20% of cord T cells after 8 days, resulting in a threefold increase in cord T cell numbers. However, the expanded cells retained a CD45RA+ CD45RO- phenotype. Similar results were obtained with adult CD45RA+ T cells. IL-7-expanded CD45RA+ RO- T cells expressed CD45RO after stimulation through the TCR. Investigations into the regulation of replicative senescence showed that after 12 days in culture with IL-7, cord blood CD45RA+ T cell proliferation resulted in telomere shortening. Nevertheless, IL-7-expanded cord blood T cells still maintained longer telomeres than unstimulated adult T cells. IL-7 but not IL-2 could directly induce high telomerase activity which probably retarded the rate of telomere shortening in cord blood T cells. These results suggest that proliferation induced by IL-7 may be important for extrathymic expansion of neonatal CD45RA+ T cells and may also contribute to the maintenance of the adult CD45RA+ T cell pool.
Soares
M V
MV
Department of Immunology, The Royal Free Hospital School of Medicine, London, United Kingdom.
Borthwick
N J
NJ
Maini
M K
MK
Janossy
G
G
Salmon
M
M
Akbar
A N
AN
D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000502:physiology; D004789:Enzyme Activation; D005312:Fetal Blood / Q000166:cytology / Q000201:enzymology / Q000276:immunology; D006706:Homeostasis / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D007231:Infant, Newborn; D015851:Interleukin-7 / Q000502:physiology*; D017493:Leukocyte Common Antigens / Q000096:biosynthesis*; D008213:Lymphocyte Activation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D015375:Receptors, Interleukin-2 / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000201:enzymology / Q000276:immunology*; D019098:Telomerase / Q000378:metabolism; D016615:Telomere / Q000201:enzymology; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology; D051020:bcl-X Protein
D000911:Antibodies, Monoclonal; C494811:BCL2L1 protein, human; D017252:CD3 Complex; D016207:Cytokines; D015851:Interleukin-7; D019253:Proto-Oncogene Proteins c-bcl-2; D015375:Receptors, Interleukin-2; D051020:bcl-X Protein; D019098:Telomerase; D017493:Leukocyte Common Antigens