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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 Cells¹

Ken’ichi Imanishi^2,*, Kazuhiro Seo^§, Hidehito Kato^*, Tohru Miyoshi-Akiyama^*, Rui-Hua Zhang^*, Yoshinori Takanashi^§, Yasuharu Imai^§ and Takehiko Uchiyama^*,,

^* Department of Microbiology and Immunology, Department of Infectious Disease Control, Institute of Laboratory Animals, and ^§ Department of Pediatric Cardiovascular Surgery, The Heart Institute of Japan, Tokyo Women’s Medical College, Tokyo, Japan

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 Vß2, 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.

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