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PMID: 8459203 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Phenotypic and functional analysis of positive selection in the gamma/delta T cell lineage.

The Journal of experimental medicine ·Vol. 177 ·No. 4 ·1993-04-01 ·Pages 1061-70

Wells FB, Tatsumi Y, Bluestone JA, Hedrick SM, Allison JP, Matis LA

Abstract

Recent evidence suggests that T cells expressing gamma/delta antigen receptors (T cell receptor [TCR]) are subject to positive selection during development. We have shown that T cells expressing a class I major histocompatibility complex (MHC)-specific gamma/delta TCR transgene (tg) are not positively selected in class I MHC-deficient, beta 2-microglobulin (beta 2m) gene knockout mice (tg+ beta 2m-). In this report, we examine phenotypic and functional parameters of gamma/delta positive selection in this transgenic model system. TCR-gamma/delta tg+ thymocytes of mature surface phenotype (heat stable antigen-, CD5hi) were found in beta 2m+ but not in beta 2m- mice. Moreover, subsets of tg+ thymocytes with the phenotype of activated T cells (interleukin [IL]2R+, CD44hi, or Mel-14lo) were also present only in the beta 2m+ mice. Cyclosporine A, which blocks positive selection of TCR-alpha/beta T cells, also inhibited gamma/delta tg+ T cell development. These results support the idea that positive selection of TCR-gamma/delta requires active TCR-mediated signal transduction. Whereas tg+ beta 2m+ thymocytes produced IL-2 and proliferated when stimulated by alloantigen, TCR engagement of tg+ beta 2m- thymocytes by antigen induced IL-2R expression but was uncoupled from the signal transduction pathway leading to IL-2 production and autocrine proliferation. Overall, these results demonstrate significant parallels between gamma/delta and alpha/beta lineage development, and suggest a general role for TCR signaling in thymic maturation.

MeSH Terms
Animals Cell Differentiation Cyclosporine/pharmacology Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Transgenic Phenotype Receptors, Antigen, T-Cell, gamma-delta/biosynthesis,genetics Signal Transduction T-Lymphocytes/cytology,metabolism Thymus Gland/cytology,drug effects,growth & development
Chemicals
Receptors, Antigen, T-Cell, gamma-delta Cyclosporine
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Wells F B
Biological Carcinogenesis and Development Program, PRI/DynCorp, Frederick, Maryland 21702-1201.
Tatsumi Y
Bluestone J A
Hedrick S M
Allison J P
Matis L A
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.177.4.1061
Published
1993-04-01
Pages
1061-70
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2190965
Subset
IM
Grants
NIAID NIH HHS · AI00602 · United States
NCI NIH HHS · CA-40041 · United States
NCI NIH HHS · N01-CO-74102 · United States
External Links
PubMed source DOI: 10.1084/jem.177.4.1061 PMC Full Text View journal details
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