Low-dose antigen-experienced CD4+ T cells display reduced clonal expansion but facilitate an effective memory pool in response to secondary exposure.
The strength and duration of an antigenic signal at the time of initial stimulation were assumed to affect the development and response of effectors and memory cells to secondary stimulation with the same antigen. To test this assumption, we used T-cell receptor (TCR)-transgenic CD4+ T cells that were stimulated in vitro with various antigen doses. The primary effector CD4+ T cells generated in response to low-dose antigen in vitro exhibited reduced clonal expansion upon secondary antigenic exposure after adoptive transfer to hosts. However, the magnitude of their contraction was much smaller than both those generated by high-dose antigen stimulation and by naïve CD4+ T cells, resulting in higher numbers of antigen-specific CD4+ T cells remaining until the memory stage. Moreover, secondary effectors and memory cells developed by secondary antigen exposure were not functionally impaired. In hosts given the low-dose antigen-experienced CD4+ T cells, we also observed accelerated recall responses upon injection of antigen-bearing antigen-presenting cells. These results suggest that primary TCR stimulation is important for developing optimal effectors during initial antigen exposure to confer long-lasting memory CD4+ T cells in response to secondary exposure.
Park
Seong Ok
SO
Department of Microbiology, College of Veterinary Medicine and Bio-Safety Research Institute, Chonbuk National University, Jeonju, Republic of Korea.
Han
Young Woo
YW
Aleyas
Abi George
AG
George
Junu Abi
JA
Yoon
Hyun A
HA
Lee
John Hwa
JH
Kang
Ho Young
HY
Kang
Seong Ho
SH
Eo
Seong Kug
SK
D019264:Adoptive Transfer; D000818:Animals; D000941:Antigens / Q000008:administration & dosage; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D004306:Dose-Response Relationship, Immunologic; D007156:Immunologic Memory / Q000276:immunology*; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology
D000941:Antigens; D016207:Cytokines; D010047:Ovalbumin