Lack of influence of cyclosporine on antigen presentation to lysozyme-specific T cell hybridomas.
Cyclosporine (CsA) was tested for its ability to inhibit antigen presentation by spleen cells or the B lymphoma line A20 to T cell hybridomas specific for hen egg-white lysozyme (HEL). Antigen-presenting cells (APC) were treated with CsA or nonimmunosuppressive derivatives thereof during or prior to encounter with antigen. The APC were then washed extensively and incubated in CsA-free medium for 6 hr before the T hybridoma cells were added. Under these conditions, CsA had no effect on antigen presentation up to the cytostatic regimen (1 microgram/ml). Omission of the 6-hr interval between CsA treatment of APC and the addition of T hybridoma resulted in inhibition of interleukin 2 production, although the CsA concentrations required were 10-75-fold higher than the ones inhibiting T cells directly (IC50: 100-150 ng/ml vs. 2-10 ng/ml). The responses to both HEL and a synthetic peptide of HEL sequence 105-120 were inhibited, indicating that the step influenced by the drug was not antigen-processing. The nonimmunosuppressive derivatives remained ineffective under these conditions. The results illustrate that the carryover of CsA from APC to T cells can mimic a drug effect on antigen presentation. Therefore, the demonstration of a CsA effect on antigen presentation can only be considered as conclusive when the readout of APC function is not a T cell response.
Muller
S
S
Preclinical Research, Sandoz Ltd., Basel, Switzerland.
Adorini
L
L
Appella
E
E
Nagy
Z A
ZA
D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects* / Q000276:immunology; D002455:Cell Division / Q000187:drug effects; D003524:Cyclosporins / Q000494:pharmacology*; D006825:Hybridomas; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects; D008211:Lymphocyte Cooperation / Q000187:drug effects*; D051379:Mice; D009113:Muramidase; D010446:Peptide Fragments / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects*
D003524:Cyclosporins; D007376:Interleukin-2; D010446:Peptide Fragments; D009113:Muramidase