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Assessing Cd8 T Cell Number and Dysfunction in the Presence of Antigen
| Content Provider | Semantic Scholar |
|---|---|
| Author | Welsh, Raymond M. |
| Copyright Year | 2001 |
| Abstract | CD8 T cells proliferate and differentiate into cytokine-secreting cytolytic effectors on encounter with viral anti-gens. As virus is cleared the activated T cells undergo apop-tosis, but some survive and enter the memory pool where they persist indefinitely, slowly dividing in a relatively qui-escent state until reactivation on reexposure to the antigen (1). The dynamics of this whole process can be variable and change as a consequence of the antigen load, the diversity of the available T cell repertoire, and the age of the host. During persistent infections, T cells and antigen coexist in an interactive environment, leading to a continued evolution of T cells that often become dysfunctional. New technologies with avidin-linked MHC tetramers, chimeric IgG–MHC dimers, and peptide-induced intracellular cy-tokine assays have allowed for the identification of multi-clonal populations of antigen-specific T cells and are now showing how T cells can be heterogeneous in their expression of surface antigens and exist in dramatically different functional states. Under certain conditions, antigen-specific T cells may lack effector activity, and under other conditions , fully functional T cells may lack reactivity with MHC tetramers or dimers, leading one to conclude that monitoring T cell responses by a single technique may lead to misconceptions of the nature of an ongoing T cell response. Functional Antigen-specific T Cells. In mice acutely infected with a moderate dose of lymphocytic choriomenin-gitis virus (LCMV), the frequencies of CD8 T cells detected by MHC tetramers and MHC dimers correlate well with the total number of activated CD8 T cells and with the frequencies of antigen-specific cells detected by peptide-induced intracellular IFN-␥ assays (2–4); these same effector cells are highly cytotoxic against targets pulsed with LCMV-encoded peptides. The frequencies of T cells that seed the memory pool are functions of the clonal burst size of T cells during the acute response (5); this burst size is very high in the LCMV system, and, as a consequence, 10– 15% of the spleen CD8 T cells remain specific for LCMV in the memory pool (2, 4). In this memory state, there remains excellent concordance among the MHC tetramer, MHC dimer, and intracellular IFN-␥ assays (2, 4). The memory pool specific for each of these LCMV epitopes remains functional and stable in the absence of immune system per-turbance, but other infections can disrupt this memory pool by displacing the LCMV-specific T cells with memory T cells of other specificities (4). Dysfunctional Antigen-specific … |
| Starting Page | f19 |
| Ending Page | f22 |
| Page Count | 4 |
| File Format | PDF HTM / HTML |
| PubMed reference number | 11238597v1 |
| Volume Number | 193 |
| Journal | The Journal of experimental medicine |
| Alternate Webpage(s) | https://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=2038&context=oapubs&httpsredir=1&referer= |
| Alternate Webpage(s) | http://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=2038&context=oapubs |
| Alternate Webpage(s) | http://jem.rupress.org/content/jem/193/5/F19.full.pdf |
| Alternate Webpage(s) | http://ftp.ncbi.nlm.nih.gov/pub/pmc/8b/1f/010156.PMC2193392.pdf |
| Alternate Webpage(s) | https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/8b/1f/010156.PMC2193392.pdf |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Avidin Cell secretion Cellular Phone Clone Genetic Heterogeneity HIV HLA Antigens Helper-Inducer T-Lymphocyte Hepatitis B Immune system Infection Leukemia, B-Cell Leukemia, T-Cell Lymphocytic choriomeningitis virus Numerous Reactivation cytokine |
| Content Type | Text |
| Resource Type | Article |