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International Immunology Advance Access published online on July 18, 2005
International Immunology, doi:10.1093/intimm/dxh298
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© The Japanese Society for Immunology. 2005. All rights reserved. For permissions, please e-mail: journals.permissions@oupjournals.org
Received December 3, 2004
Accepted June 17, 2005

Article

Human peripheral CD2-/lo T cells: an extrathymic population of early differentiated, developing T cells

Matthew J. Loza 1, Patrizia Luppi 2, Kerstin Kiefer 3, Eric S. Martin 3, Jennifer L. Szczytkowski 3, and Bice Perussia 3*

1 Department of Microbiology and Immunology, Kimmel Cancer Center, Jefferson Medical College, Thomas Jefferson University; BLSB 750, 233 South, 10th Street, Philadelphia, PA 19107, USA; Present address: Wake Forest University School of Medicine
2 Department of Pediatrics, Division of Immunogenetics, Rangos Research Center, University of Pittsburgh Medical School, Pittsburgh, PA 15213, USA
3 Department of Microbiology and Immunology, Kimmel Cancer Center, Jefferson Medical College, Thomas Jefferson University; BLSB 750, 233 South, 10th Street, Philadelphia, PA 19107, USA

* To whom correspondence should be addressed.
Bice Perussia, E-mail: bice.perussia{at}mail.tju.edu


  Abstract

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 (V{beta} 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.

Keywords: CD2; differentiation; T-cell receptor repertoire; T-cell subset.
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