Physiological relevance of antigen presentasome (APS), an acquired MHC/costimulatory complex, in the sustained activation of CD4+ T cells in the absence of APCs.
T-cell interaction with antigen-presenting cells (APCs) results in activation and clonal expansion of naive T cells. CD80 expression/acquisition in T cells has been implicated in disease processes in patients with rheumatoid arthritis and multiple myeloma and patients infected with HIV. Our previous data indicate that antigen-specific activation of naive T cells results in T-cell acquisition of CD80 molecules from APCs. However, the functional relevance of the acquired CD80 by T cells in signal pathways has remained unresolved. This study aims to define for the first time the role of acquired CD80 in T-cell clonal expansion. We demonstrate the following: (1) T cells, upon CD80 acquisition, sustain their proliferative response in the absence of APCs; (2) T cells that acquire CD80 sustain the activity of transcriptional factors such as nuclear factor-kappaB (NFkappaB) and activator protein-1 (AP1) for 24 hours after separation from APCs and up-regulate signal transducer and activator of transcription-5 (Stat5) in the absence of APCs or exogenous signal 1; and (3) maintenance of these signals results in unique cytokine production. Collectively, our data support the unique concept that naive T cells sustain their activation by removing "antigen presentasome" (APS; eg, antigen-presenting complex) from APCs, thereby releasing the constraint of APC requirement for further activation.
Zhou
Jun
J
Laboratory of Tumor Immunology and Biology, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA.
Tagaya
Yutaka
Y
Tolouei-Semnani
Roshanak
R
Schlom
Jeffrey
J
Sabzevari
Helen
H
D000818:Animals; D017951:Antigen Presentation / Q000502:physiology*; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000502:physiology*; D018122:B7-1 Antigen / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D010856:Columbidae; D045304:Cytochromes c / Q000235:genetics; D016207:Cytokines / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D007700:Kinetics; D008285:Major Histocompatibility Complex / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D015398:Signal Transduction / Q000276:immunology
D018122:B7-1 Antigen; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D045304:Cytochromes c