Differential regulation of interleukin 2 (IL-2) receptor expression on antigen-specific human T cell clones by IL-2.
A panel of human T cell clones bearing exclusively the T4 (helper) phenotype and demonstrating specificity to a well-characterized soluble glycoprotein antigen (185,000 dalton streptococcal antigen, SA) is described. After having been cultured in exogenous interleukin 2 (IL-2) for 7 days in the absence of the specific antigen, two of the clones, namely SA1.4 and SA1.23, show stronger proliferative responses to the ligand as compared to the other T4 clones. Analysis of both the high- and low-affinity IL-2 receptor (IL-2R) levels reveals that IL-2 mediates differential regulation of high affinity IL-2R expression on these antigen-deprived cloned cells. Higher levels of surface expression of the IL-2 binding sites on SA1.4 and SA1.23 as compared to the other clones are observed throughout the 7-day culture period that these lymphocytes are maintained in exogenous IL-2. All the cloned cells appear to have returned to their "unstimulated states" as noted by their stable low expressions of Tac antigen and high affinity IL-2R. The unstimulated states of SA1.4 and SA1.23 are represented by higher levels of high affinity IL-2R expression. Under the condition in which the cloned cells are exposed to a decreasing concentration of IL-2, SA1.4 and SA1.23 are found to secrete a greater amount of IFN-gamma. The present results therefore suggest that a control mechanism involving the "mutual amplification" of IL-2 and IFN-gamma regulates the differential expression of high affinity IL-2R on antigen-specific T4 clones.
D000942:Antigens, Bacterial / Q000276:immunology; D000954:Antigens, Surface / Q000378:metabolism*; D002455:Cell Division; D002478:Cells, Cultured; D002999:Clone Cells; D000939:Epitopes; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism*; D015375:Receptors, Interleukin-2; D013291:Streptococcus; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7
D000942:Antigens, Bacterial; D000954:Antigens, Surface; D000939:Epitopes; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7