Human peripheral CD2-/lo T cells: an extrathymic population of early differentiated, developing T cells.
We previously reported that a subset of human peripheral blood CD3+ T cells expresses low-to-null CD2 levels (CD2-/lo), produces type 2 cytokines and is inducible to differentiate to functionally mature IFN-gamma+ cells. Multiple-color immunofluorescence analysis indicated that this population, representing <0.1% of the T cells in fresh lymphocytes, contains subsets that are phenotypically immature, including CD4-CD8- and CD3+TCR- cells. Ex vivo, the CD2-/lo cells can proliferate (carboxyfluorescein diacetate succinimidyl ester analysis) independently from exogenous stimulation, respond to CD3-mediated stimulation with significantly greater proliferation than the autologous mature cells and their subsets are inducible to undergo in vitro a developmental sequence similar to that reported for the phenotypically similar thymic populations. This is especially evident for the CD4+CD8+ subset. CD2-/lo T-cell populations exhibit a TCR repertoire (Vbeta chain distribution) that is complete but different (complementarity determining region R3 analysis) from that of the autologous CD2+ T cells. These characteristics distinguish peripheral CD2-/lo T cells as possible early differentiated T cells that may undergo extrathymic maturation, and potentially contribute to maintain the peripheral naive T-cell pool. These findings define the existence of phenotypically immature T cells in the periphery. Also, given the high numbers of CD2-/lo T cells generated, upon ex vivo culture, from peripheral lymphocytes of all adult and neonatal individuals tested, they have relevance to clinical applications for immune reconstitution of T cells, as well as myeloid cells, via myeloid colony-stimulating factors and type 2 cytokines.
Loza
Matthew J
MJ
Department of Microbiology and Immunology, Kimmel Cancer Center, Jefferson Medical College, Thomas Jefferson University, BLSB 750, 233 South, 10th Street, Philadelphia, PA 19107, USA.
Luppi
Patrizia
P
Kiefer
Kerstin
K
Martin
Eric S
ES
Szczytkowski
Jennifer L
JL
Perussia
Bice
B
D000328:Adult; D018801:CD2 Antigens / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology*; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology
D018801:CD2 Antigens; D017252:CD3 Complex