FcγRII/III and CD2 expression mark distinct subpopulations of immature CD4-CD8-murine thymocytes: In vivo developmental kinetics and T cell receptor β chain rearrangement status

Hans Reimer Rodewald, Katherine Awad, Philippe Moingeon, Luciano D'Adamio, Daniel Rabinowitz, Yoichi Shinkai, Frederick W. Alt, Ellis L. Reinherz

Research output: Contribution to journalArticle

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Abstract

We have recently identified a dominant wave of CD4-CD8- (double-negative [DN]) thymocytes in early murine fetal development that express low affinity Fcγ receptors (FcγRII/III) and contain precursors for Tiα/β lineage T cells. Here we show that FcγRII/III is expressed in very immature CD4low single-positive (SP) thymocytes and that FcγRII/III expression is downregulated within the DN subpopulation and before the CD3-CD8low SP stage in T cell receptor (TCR)-α/β lineage-committed thymocytes. DN FcγRII/III+ thymocytes also contain a small fraction of TCR-γ/δ lineage cells in addition to TCR-α/β progenitors. Fetal day 15.5 DN TCR-α/β lineage progenitors can be subdivided into three major subpopulations as characterized by cell surface expression of FcγRII/III vs. CD2 (FcγRII/III+CD2-, FcγRII/ III+CD2+, FcγRII/III-CD2+). Phenotypic analysis during fetal development as well as adoptive transfer of isolated fetal thymocyte subpopulations derived from C57B1/6 (Ly5.1) mice into normal nonirradiated Ly5.2 congenic recipient mice identifies one early differentiation sequence (FcγRII/III+CD2- → FcγRII/III+CD2+ → FcγRII/III- CD2+) that precedes the entry of DN thymocytes into the CD4+CD8+ double-positive (DP) TCRlow/- stage. Unseparated day 15.5 fetal thymocytes develop into DP thymocytes within 2.5 d and remain at the DP stage for >48 h before being selected into either CD4+ or CD8+ SP thymocytes. In contrast, FcγRII/ III+CD2- DN thymocytes follow this same developmental pathway but are delayed by ∼24 h before entering the DP compartment, while FcγRII/III-CD2+ display accelerated development by ∼24 h compared with total day 15.5 thymocytes. FcγRII/III-CD2+ are also more developmentally advanced than FcγRII/III+CD2- fetal thymocytes with respect to their TCR β chain V(D)J rearrangement. At day 15.5 in gestation, β chain V(D)J rearrangement is mostly, if not entirely, restricted to the FcγRII/III-CD2+ subset of DN fetal thymocytes. Consistent with this analysis in fetal thymocytes, >90% of adult thymocytes derived from mice carrying a disrupting mutation at the recombination-activating gene 2 locus (RAG-2-/-) on both alleles are developmentally arrested at the DN CD2- stage. In addition, there is a fivefold increase in the relative percentage of thymocytes expressing FcγRII/III in TCR and immunoglobulin gene rearrangement-incompetent homozygous RAG-2-/- mice (15% FcγRII/III+) versus rearrangement-competent heterozygous RAG-2+/- mice (<3% FcγRII/III+). Thus, FcγRII/III expression defines an early DN stage preceding Vβ(Dβ)Jβ rearrangement, which in turn is followed by surface expression of CD2. Loss of FcγRII/III and acquisition of CD2 expression characterize a late DN stage immediately before the conversion into DP thymocytes.

Original languageEnglish (US)
Pages (from-to)1079-1092
Number of pages14
JournalJournal of Experimental Medicine
Volume177
Issue number4
StatePublished - Apr 1 1993
Externally publishedYes

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Thymocytes
T-Cell Antigen Receptor
Cell Lineage
Fetal Development
Congenic Mice
T-Cell Receptor Genes
Immunoglobulin Genes
Adoptive Transfer
Fc Receptors
Gene Rearrangement
Genetic Recombination

ASJC Scopus subject areas

  • Immunology

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FcγRII/III and CD2 expression mark distinct subpopulations of immature CD4-CD8-murine thymocytes : In vivo developmental kinetics and T cell receptor β chain rearrangement status. / Rodewald, Hans Reimer; Awad, Katherine; Moingeon, Philippe; D'Adamio, Luciano; Rabinowitz, Daniel; Shinkai, Yoichi; Alt, Frederick W.; Reinherz, Ellis L.

In: Journal of Experimental Medicine, Vol. 177, No. 4, 01.04.1993, p. 1079-1092.

Research output: Contribution to journalArticle

Rodewald, HR, Awad, K, Moingeon, P, D'Adamio, L, Rabinowitz, D, Shinkai, Y, Alt, FW & Reinherz, EL 1993, 'FcγRII/III and CD2 expression mark distinct subpopulations of immature CD4-CD8-murine thymocytes: In vivo developmental kinetics and T cell receptor β chain rearrangement status', Journal of Experimental Medicine, vol. 177, no. 4, pp. 1079-1092.
Rodewald, Hans Reimer ; Awad, Katherine ; Moingeon, Philippe ; D'Adamio, Luciano ; Rabinowitz, Daniel ; Shinkai, Yoichi ; Alt, Frederick W. ; Reinherz, Ellis L. / FcγRII/III and CD2 expression mark distinct subpopulations of immature CD4-CD8-murine thymocytes : In vivo developmental kinetics and T cell receptor β chain rearrangement status. In: Journal of Experimental Medicine. 1993 ; Vol. 177, No. 4. pp. 1079-1092.
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abstract = "We have recently identified a dominant wave of CD4-CD8- (double-negative [DN]) thymocytes in early murine fetal development that express low affinity Fcγ receptors (FcγRII/III) and contain precursors for Tiα/β lineage T cells. Here we show that FcγRII/III is expressed in very immature CD4low single-positive (SP) thymocytes and that FcγRII/III expression is downregulated within the DN subpopulation and before the CD3-CD8low SP stage in T cell receptor (TCR)-α/β lineage-committed thymocytes. DN FcγRII/III+ thymocytes also contain a small fraction of TCR-γ/δ lineage cells in addition to TCR-α/β progenitors. Fetal day 15.5 DN TCR-α/β lineage progenitors can be subdivided into three major subpopulations as characterized by cell surface expression of FcγRII/III vs. CD2 (FcγRII/III+CD2-, FcγRII/ III+CD2+, FcγRII/III-CD2+). Phenotypic analysis during fetal development as well as adoptive transfer of isolated fetal thymocyte subpopulations derived from C57B1/6 (Ly5.1) mice into normal nonirradiated Ly5.2 congenic recipient mice identifies one early differentiation sequence (FcγRII/III+CD2- → FcγRII/III+CD2+ → FcγRII/III- CD2+) that precedes the entry of DN thymocytes into the CD4+CD8+ double-positive (DP) TCRlow/- stage. Unseparated day 15.5 fetal thymocytes develop into DP thymocytes within 2.5 d and remain at the DP stage for >48 h before being selected into either CD4+ or CD8+ SP thymocytes. In contrast, FcγRII/ III+CD2- DN thymocytes follow this same developmental pathway but are delayed by ∼24 h before entering the DP compartment, while FcγRII/III-CD2+ display accelerated development by ∼24 h compared with total day 15.5 thymocytes. FcγRII/III-CD2+ are also more developmentally advanced than FcγRII/III+CD2- fetal thymocytes with respect to their TCR β chain V(D)J rearrangement. At day 15.5 in gestation, β chain V(D)J rearrangement is mostly, if not entirely, restricted to the FcγRII/III-CD2+ subset of DN fetal thymocytes. Consistent with this analysis in fetal thymocytes, >90{\%} of adult thymocytes derived from mice carrying a disrupting mutation at the recombination-activating gene 2 locus (RAG-2-/-) on both alleles are developmentally arrested at the DN CD2- stage. In addition, there is a fivefold increase in the relative percentage of thymocytes expressing FcγRII/III in TCR and immunoglobulin gene rearrangement-incompetent homozygous RAG-2-/- mice (15{\%} FcγRII/III+) versus rearrangement-competent heterozygous RAG-2+/- mice (<3{\%} FcγRII/III+). Thus, FcγRII/III expression defines an early DN stage preceding Vβ(Dβ)Jβ rearrangement, which in turn is followed by surface expression of CD2. Loss of FcγRII/III and acquisition of CD2 expression characterize a late DN stage immediately before the conversion into DP thymocytes.",
author = "Rodewald, {Hans Reimer} and Katherine Awad and Philippe Moingeon and Luciano D'Adamio and Daniel Rabinowitz and Yoichi Shinkai and Alt, {Frederick W.} and Reinherz, {Ellis L.}",
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TY - JOUR

T1 - FcγRII/III and CD2 expression mark distinct subpopulations of immature CD4-CD8-murine thymocytes

T2 - In vivo developmental kinetics and T cell receptor β chain rearrangement status

AU - Rodewald, Hans Reimer

AU - Awad, Katherine

AU - Moingeon, Philippe

AU - D'Adamio, Luciano

AU - Rabinowitz, Daniel

AU - Shinkai, Yoichi

AU - Alt, Frederick W.

AU - Reinherz, Ellis L.

PY - 1993/4/1

Y1 - 1993/4/1

N2 - We have recently identified a dominant wave of CD4-CD8- (double-negative [DN]) thymocytes in early murine fetal development that express low affinity Fcγ receptors (FcγRII/III) and contain precursors for Tiα/β lineage T cells. Here we show that FcγRII/III is expressed in very immature CD4low single-positive (SP) thymocytes and that FcγRII/III expression is downregulated within the DN subpopulation and before the CD3-CD8low SP stage in T cell receptor (TCR)-α/β lineage-committed thymocytes. DN FcγRII/III+ thymocytes also contain a small fraction of TCR-γ/δ lineage cells in addition to TCR-α/β progenitors. Fetal day 15.5 DN TCR-α/β lineage progenitors can be subdivided into three major subpopulations as characterized by cell surface expression of FcγRII/III vs. CD2 (FcγRII/III+CD2-, FcγRII/ III+CD2+, FcγRII/III-CD2+). Phenotypic analysis during fetal development as well as adoptive transfer of isolated fetal thymocyte subpopulations derived from C57B1/6 (Ly5.1) mice into normal nonirradiated Ly5.2 congenic recipient mice identifies one early differentiation sequence (FcγRII/III+CD2- → FcγRII/III+CD2+ → FcγRII/III- CD2+) that precedes the entry of DN thymocytes into the CD4+CD8+ double-positive (DP) TCRlow/- stage. Unseparated day 15.5 fetal thymocytes develop into DP thymocytes within 2.5 d and remain at the DP stage for >48 h before being selected into either CD4+ or CD8+ SP thymocytes. In contrast, FcγRII/ III+CD2- DN thymocytes follow this same developmental pathway but are delayed by ∼24 h before entering the DP compartment, while FcγRII/III-CD2+ display accelerated development by ∼24 h compared with total day 15.5 thymocytes. FcγRII/III-CD2+ are also more developmentally advanced than FcγRII/III+CD2- fetal thymocytes with respect to their TCR β chain V(D)J rearrangement. At day 15.5 in gestation, β chain V(D)J rearrangement is mostly, if not entirely, restricted to the FcγRII/III-CD2+ subset of DN fetal thymocytes. Consistent with this analysis in fetal thymocytes, >90% of adult thymocytes derived from mice carrying a disrupting mutation at the recombination-activating gene 2 locus (RAG-2-/-) on both alleles are developmentally arrested at the DN CD2- stage. In addition, there is a fivefold increase in the relative percentage of thymocytes expressing FcγRII/III in TCR and immunoglobulin gene rearrangement-incompetent homozygous RAG-2-/- mice (15% FcγRII/III+) versus rearrangement-competent heterozygous RAG-2+/- mice (<3% FcγRII/III+). Thus, FcγRII/III expression defines an early DN stage preceding Vβ(Dβ)Jβ rearrangement, which in turn is followed by surface expression of CD2. Loss of FcγRII/III and acquisition of CD2 expression characterize a late DN stage immediately before the conversion into DP thymocytes.

AB - We have recently identified a dominant wave of CD4-CD8- (double-negative [DN]) thymocytes in early murine fetal development that express low affinity Fcγ receptors (FcγRII/III) and contain precursors for Tiα/β lineage T cells. Here we show that FcγRII/III is expressed in very immature CD4low single-positive (SP) thymocytes and that FcγRII/III expression is downregulated within the DN subpopulation and before the CD3-CD8low SP stage in T cell receptor (TCR)-α/β lineage-committed thymocytes. DN FcγRII/III+ thymocytes also contain a small fraction of TCR-γ/δ lineage cells in addition to TCR-α/β progenitors. Fetal day 15.5 DN TCR-α/β lineage progenitors can be subdivided into three major subpopulations as characterized by cell surface expression of FcγRII/III vs. CD2 (FcγRII/III+CD2-, FcγRII/ III+CD2+, FcγRII/III-CD2+). Phenotypic analysis during fetal development as well as adoptive transfer of isolated fetal thymocyte subpopulations derived from C57B1/6 (Ly5.1) mice into normal nonirradiated Ly5.2 congenic recipient mice identifies one early differentiation sequence (FcγRII/III+CD2- → FcγRII/III+CD2+ → FcγRII/III- CD2+) that precedes the entry of DN thymocytes into the CD4+CD8+ double-positive (DP) TCRlow/- stage. Unseparated day 15.5 fetal thymocytes develop into DP thymocytes within 2.5 d and remain at the DP stage for >48 h before being selected into either CD4+ or CD8+ SP thymocytes. In contrast, FcγRII/ III+CD2- DN thymocytes follow this same developmental pathway but are delayed by ∼24 h before entering the DP compartment, while FcγRII/III-CD2+ display accelerated development by ∼24 h compared with total day 15.5 thymocytes. FcγRII/III-CD2+ are also more developmentally advanced than FcγRII/III+CD2- fetal thymocytes with respect to their TCR β chain V(D)J rearrangement. At day 15.5 in gestation, β chain V(D)J rearrangement is mostly, if not entirely, restricted to the FcγRII/III-CD2+ subset of DN fetal thymocytes. Consistent with this analysis in fetal thymocytes, >90% of adult thymocytes derived from mice carrying a disrupting mutation at the recombination-activating gene 2 locus (RAG-2-/-) on both alleles are developmentally arrested at the DN CD2- stage. In addition, there is a fivefold increase in the relative percentage of thymocytes expressing FcγRII/III in TCR and immunoglobulin gene rearrangement-incompetent homozygous RAG-2-/- mice (15% FcγRII/III+) versus rearrangement-competent heterozygous RAG-2+/- mice (<3% FcγRII/III+). Thus, FcγRII/III expression defines an early DN stage preceding Vβ(Dβ)Jβ rearrangement, which in turn is followed by surface expression of CD2. Loss of FcγRII/III and acquisition of CD2 expression characterize a late DN stage immediately before the conversion into DP thymocytes.

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