Post-thymic maturation of migrating human thymic single-positive T cells: thymic CD1a- CD4+ T cells are more susceptible to anergy induction by toxic shock syndrome toxin-1 than cord blood CD4+ T cells.
To determine whether human CD4+ T cells undergo post-thymic maturation, we compared the susceptibility to anergy induction in human thymic CD1a- CD4+ single-positive (CD4+), cord blood (CB) CD4+, and adult peripheral blood (APB) CD4+ T cells by stimulation with toxic shock syndrome toxin-1 (TSST-1). Most TSST-1-induced T cell blasts derived from either T cell preparation expressed TCR Vbeta2, which determines the potential reactivity to TSST-1. Most thymic CD4+ T cell blast preparations exhibited little or no production of IL-2 and IL-4 after restimulation with TSST-1 and only marginal responses after stimulation with rIL-2 or a combination of PMA and calcium ionophore, while the APB CD4+ T cell blasts showed high responses to these stimuli. The responses of CB CD4+ T cell blasts to these stimuli varied, ranging from minimal to relatively high. Studies of DNA fragmentation showed that there was no significant cell death of thymic CD4+ T cell blasts. Most thymic CD1a- CD4+ and CB CD4+ T cells were CD38 positive. APB CD4+ T cell blasts derived from the CD38+ fraction and from the CD38- fraction exhibited equally high responses to restimulation with TSST-1. These results indicate that thymic CD1a- CD4+ and CB CD4+ T cells are inherently highly susceptible to anergy induction by bacterial superantigens and that thymic CD1a- CD4+ T cells are less mature than CB CD4+ T cells, suggesting that post-thymic maturation in thymic T cells migrating to the periphery is required for acquisition of full reactivity to antigenic stimulation.
Imanishi
K
K
Department of Microbiology and Immunology, The Heart Institute of Japan, Tokyo Women's Medical College, Japan.
Seo
K
K
Kato
H
H
Miyoshi-Akiyama
T
T
Zhang
R H
RH
Takanashi
Y
Y
Imai
Y
Y
Uchiyama
T
T
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000293:Adolescent; D000328:Adult; D015703:Antigens, CD; D018949:Antigens, CD1 / Q000032:analysis; D000943:Antigens, Differentiation / Q000032:analysis; D001427:Bacterial Toxins; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002470:Cell Survival; D002648:Child; D002675:Child, Preschool; D017635:Clonal Anergy; D004768:Enterotoxins / Q000633:toxicity*; D005312:Fetal Blood / Q000166:cytology*; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D007376:Interleukin-2 / Q000096:biosynthesis / Q000494:pharmacology; D015847:Interleukin-4 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins; D009244:NAD+ Nucleosidase / Q000032:analysis; D018089:Superantigens; D018418:Th2 Cells / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology*
D015703:Antigens, CD; D018949:Antigens, CD1; D000943:Antigens, Differentiation; D001427:Bacterial Toxins; D004768:Enterotoxins; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D018089:Superantigens; C030107:enterotoxin F, Staphylococcal; D015847:Interleukin-4; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1