The majority of postselection CD4+ single-positive thymocytes requires the thymus to produce long-lived, functional T cells

Rubendra Dyall, Janko Nikolich-Zugich

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52 Citations (Scopus)

Abstract

We have previously isolated, and characterized in vitro, two subsets of CD4(hi) T cell receptor (TCR)(hi) single positive (SP) thymocytes: CD8- and CD8(lo). In this report, we have analyzed phenotypic, functional, and developmental characteristics of these 'late' CD4(hi) SP thymocyte subsets. The TCR(hi) phenotype and the elimination of T cells expressing TCR V(β) segments reactive with endogenous mouse mammary tumor virus (MMTV) products suggested that both subsets had undergone positive and negative selection. CD8-4(hi) thymocytes were functional, as judged by their ability to: (a) induce lethal graft versus host disease (GVHD); (b) survive and expand in peripheral lymphoid organs; and (c) proliferate, rather than undergo apoptosis, in response to in vitro TCR cross-linking. By contrast, CD8(lo)4(hi) cells could not induce GVHD, were unable to expand (and perhaps even survive) in peripheral organs and underwent apoptosis upon TCR cross- linking. However, when reintroduced into the thymus, these cells matured into functional, long-lived CD8-4(hi) lymphocytes. These results document an obligatory requirement for the thymic microenvironment in the final maturation of the majority of CD4(hi) SP postselection thymocytes, and demonstrate the existence of a previously unrecognized control point in T cell development.

Original languageEnglish (US)
Pages (from-to)235-245
Number of pages11
JournalJournal of Experimental Medicine
Volume181
Issue number1
DOIs
StatePublished - Jan 1 1995
Externally publishedYes

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Thymocytes
T-Cell Antigen Receptor
Thymus Gland
T-Lymphocytes
Graft vs Host Disease
Apoptosis
Mouse mammary tumor virus
Lymphocytes
Phenotype
In Vitro Techniques

ASJC Scopus subject areas

  • Immunology

Cite this

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abstract = "We have previously isolated, and characterized in vitro, two subsets of CD4(hi) T cell receptor (TCR)(hi) single positive (SP) thymocytes: CD8- and CD8(lo). In this report, we have analyzed phenotypic, functional, and developmental characteristics of these 'late' CD4(hi) SP thymocyte subsets. The TCR(hi) phenotype and the elimination of T cells expressing TCR V(β) segments reactive with endogenous mouse mammary tumor virus (MMTV) products suggested that both subsets had undergone positive and negative selection. CD8-4(hi) thymocytes were functional, as judged by their ability to: (a) induce lethal graft versus host disease (GVHD); (b) survive and expand in peripheral lymphoid organs; and (c) proliferate, rather than undergo apoptosis, in response to in vitro TCR cross-linking. By contrast, CD8(lo)4(hi) cells could not induce GVHD, were unable to expand (and perhaps even survive) in peripheral organs and underwent apoptosis upon TCR cross- linking. However, when reintroduced into the thymus, these cells matured into functional, long-lived CD8-4(hi) lymphocytes. These results document an obligatory requirement for the thymic microenvironment in the final maturation of the majority of CD4(hi) SP postselection thymocytes, and demonstrate the existence of a previously unrecognized control point in T cell development.",
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