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Non‐responsiveness of antigen‐experienced CD4 T cells reflects more stringent co‐stimulatory requirements
Author(s) -
Maaike E. Hamel,
E Noteboom,
A M Kruisbeek
Publication year - 1998
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.1998.00443.x
Subject(s) - cd28 , cytotoxic t cell , biology , antigen , monoclonal antibody , cd3 , t cell , t lymphocyte , t cell receptor , antigen presenting cell , interleukin 21 , immunology , microbiology and biotechnology , antibody , immune system , in vitro , cd8 , biochemistry
We recently reported that previously activated T cells, irrespective of the nature of the first stimulus they encountered, are unable to respond to Staphylococcal enterotoxin B (SEB), nor to soluble anti‐CD3 monoclonal antibody (mAb) presented by splenic antigen‐presenting cells (APC). Such previously activated T cells are, however, fully capable of responding to plate‐bound anti‐CD3 plus splenic APC. These data suggest differential integration of the T‐cell receptor (TCR) and co‐stimulatory signalling pathways in naive versus antigen‐experienced T cells. Consistent with this hypothesis, anti‐CD28 mAb restores the proliferative capacity of resting ex vivo CD45RB lo CD4 + T cells (representing previously activated T cells) to both soluble anti‐CD3 mAb and SEB. Interestingly, mAb‐mediated engagement of cytotoxic T‐lymphocyte antigen‐4 (CTLA‐4) completely negates the rescue effects mediated by anti‐CD28 mAb in CD45RB lo cells. Nevertheless, the non‐responsiveness of CD45RB lo CD4 + T cells cannot be reversed by anti‐CTLA‐4 Fab fragments, indicating that it is not related to negative regulatory effects of CTLA‐4 engagement itself. Interestingly, the addition of interleukin‐2 (IL‐2) restores the proliferative capacity of CD45RB lo CD4 + T cells to SEB and soluble anti‐CD3 mAb. Moreover, when rescued by IL‐2, the cells are less susceptible to the negative regulatory effects of CTLA‐4 engagement. Together, these findings suggest that the non‐responsiveness of CD45RB lo CD4 + T cells to certain stimuli may be related to inadequate TCR signalling, primarily affecting IL‐2 production.