Regulatory CD4 T Cells Control the Size of the Peripheral Activated/Memory CD4 T Cell Compartment

• Published in: The Journal of immunology (1950) Vol. 164; no. 7; pp. 3573 - 3580
• Main Authors: Annacker, Oliver, Burlen-Defranoux, Odile, Pimenta-Araujo, Ricardo, Cumano, Ana, Bandeira, Antonio
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01.04.2000
• Subjects: Age Factors; Animals; Animals, Newborn - growth & development; Animals, Newborn - immunology; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD4-Positive T-Lymphocytes - transplantation; CD45RB antigen; Germ-Free Life - immunology; Immunologic Memory - immunology; Inflammatory Bowel Diseases - immunology; Interphase - immunology; Leukocyte Common Antigens - biosynthesis; Lymphocyte Activation - immunology; Lymphocyte Transfusion; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, SCID; Organ Specificity - immunology; Spleen - cytology; Spleen - immunology; T-Lymphocyte Subsets - cytology; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.164.7.3573

The mechanisms leading to stable T cell numbers in the periphery of a healthy animal are, to date, not well understood. We followed the expansion of CD45RBhigh (naive) and CD45RBlow (activated/memory) CD4 T cells transferred from normal mice into syngeneic Rag-20/0 recipients and the dynamics of peripheral reconstitution when both populations were coinjected. Naive cells acquired an activated phenotype and showed a high proliferative capacity that was dependent on the environment in which the recipients were kept (specific pathogen-free vs conventional housing conditions), the age of the recipients, and the presence of CD45RBlow T cells in the injected cohort. CD45RBlow CD4 T cells protected the host from CD45RBhigh CD4 T cell-induced inflammatory bowel disease and showed a limited degree of expansion. CD45RBlow CD4 T cells isolated from GF mice also showed the ability to prevent inflammatory bowel disease, indicating that at least part of the natural regulatory T cells are self-reactive. The results indicate that 1) peripheral T cell expansion in lymphocyte-deficient recipients represent classical immune responses, which are mainly promoted by exogenous Ags and 2) natural regulatory T cells control the size of the activated/memory peripheral CD4 T cell compartment.