Cell Surface CD28 Levels Define Four CD4+ T Cell Subsets: Abnormal Expression in Rheumatoid Arthritis
| Autor: | Isabel Mérida, Antonio de la Hera, Luis Villa, Eva Sanz, Laura-Inés Salazar-Fontana, Melchor Alvarez-Mon, Carlos Martínez-A, A. Zea, Ana Sánchez-Atrio |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
CD4-Positive T-Lymphocytes
medicine.medical_specialty CD3 Immunology chemical and pharmacologic phenomena In Vitro Techniques Biology Lymphocyte Activation Immune tolerance Arthritis Rheumatoid CD28 Antigens T-Lymphocyte Subsets Internal medicine Immune Tolerance medicine Humans Immunology and Allergy RNA Messenger Receptor DNA Primers CD86 Base Sequence Synovial Membrane CD28 Receptors Interleukin-2 hemic and immune systems Up-Regulation Endocrinology CTLA-4 Case-Control Studies biology.protein Interleukin-2 Leukocyte Common Antigens CD5 CD80 |
| Zdroj: | Clinical Immunology. 99:253-265 |
| ISSN: | 1521-6616 |
| DOI: | 10.1006/clim.2001.5003 |
| Popis: | CD28 is a costimulatory receptor expressed in most CD4(+) T cells. Despite the long-standing evidence for up- and downregulation of surface CD28 expression in vitro, and the key regulatory role assigned to the upregulation of CD28 counterreceptor [the CD152 (CTLA-4) molecule], in vivo CD28 induction has attracted little attention. We studied CD28 and CD152 expression and function in 33 rheumatoid arthritis (RA) patients, 20 clinically active and 13 inactive, and in 24 healthy donors. Four subsets of CD28(-), CD28(low), CD28(int), and CD28(high) peripheral blood human CD4(+) T cells were defined using three-color flow cytometry. The three CD28(+) subsets displayed a one-, two-, or threefold quantitative difference in their relative number of CD28 antibody binding sites, respectively (P < 0.01). RA patients, whether active or inactive, showed a distinct phenotype when compared to healthy donors: (i) the percentage of CD4(+)CD28(high) cells was increased twofold and the CD4(+)CD28(low) subset was reduced twofold (P < 0.01) and (ii) the CD4(+)CD28(high) cells from RA patients showed an in vivo activated phenotype, CD45RO(+)CD5(high)IL-2Ralpha(+) (P < 0.01). Active RA patients were different from inactive patients. They showed a twofold increase in mean CD28 expression (P < 0.05), whereas each of the CD28(+) subsets in the inactive RA patients showed reduced expression when compared to healthy donors. Notably, both active and inactive RA patients showed abnormal CD28 upregulation when T cells were activated in vitro with CD3 antibodies, but only inactive RA patients showed a hypoproliferative response to TCR/CD3 triggering when compared to healthy donors (P < 0.01). This defective proliferation was normalized by concurrent crosslinking with CD28 antibody. No differences were noted in the expression of CD152 or CD80, a CD28 and CD152 shared ligand. The disregulated in vivo expression of CD28 was related to the RA patients' disease activity and suggests that modulation of CD28 surface levels may be an additional mechanism to finely tune the delicate responsiveness/tolerance balance. |
| Databáze: | OpenAIRE |
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