Overlap between molecular markers expressed by naturally occurring CD4 +CD25 + regulatory T cells and antigen specific CD4 +CD25 + and CD8 +CD28 − T suppressor cells

• Published in: Human immunology Vol. 65; no. 11; pp. 1297 - 1306
• Main Authors: Scotto, Luigi, Naiyer, Afzal Jamal, Galluzzo, Sara, Rossi, Paola, Manavalan, John Sanil, Kim-Schulze, Seunghee, Fang, Jianshe, Favera, Riccardo Dalla, Cortesini, Raffaello, Suciu-Foca, Nicole
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2004
• Subjects: Biomarkers - metabolism; CD28 Antigens - immunology; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Cell Line; DNA-Binding Proteins - genetics; Forkhead Transcription Factors; Gene Expression Profiling; Humans; Isoantigens - immunology; L-Selectin - immunology; Receptors, Interleukin-2 - immunology; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism
• ISSN: 0198-8859; 1879-1166
• DOI: 10.1016/j.humimm.2004.09.004

Alloantigen specific CD8 +CD28 − T suppressor (T S) cells differ from naturally occurring CD4 +CD25 + T-regulatory (natural T R) cells not only by their phenotype but also by their mechanism of action. Natural T R have been extensively studied, leading to the identification of characteristic “molecular markers” such as Forkhead box P3 (FOXP3), glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4). We have investigated the expression of these genes in alloantigen specific T S and CD4 +CD25 + T regulatory (T R) cells and found that they are expressed at levels similar to those observed in natural T R. Furthermore, similar to natural CD4 +CD25 + T R, antigen-specific CD8 +CD28 −CD62L + T S cells have more suppressive capacity than CD8 +CD28 −CD62L − T S cells. In spite of these similarities, natural T R are not antigen-specific and inhibit other T cells by T cell-to-T cell interaction, whereas T S are antigen-specific and exert their inhibitory function by interacting with antigen-presenting cells and render them tolerogenic to other T cells. The molecular characterization of T S cells may contribute to a better understanding of mechanisms involved in inhibition of immune responses in autoimmunity, transplantation, and chronic viral infection.