Depressed in vitro T cell responses concomitant with augmented interleukin-2 responses by lymphocytes from cancer patients following in vivo treatment with interleukin-2.
Peripheral blood lymphocytes obtained from cancer patients receiving interleukin-2 (IL-2) on two separate clinical protocols were evaluated for their in vitro responses to IL-2, alloantigens, and PHA. IL-2 in vivo induced enhanced in vitro proliferative responses to IL-2 and diminished in vitro proliferative responses to phytohemagglutinin (PHA) and alloantigens. Alloinduced cytotoxic T cell responses were also depressed following in vivo IL-2. We examined the kinetics of the in vitro proliferative response to PHA and IL-2 and found that while the response of lymphocytes primed in vivo with IL-2 to PHA was depressed at all times during the 2 week in vitro exposure, the response to IL-2 peaked earlier and higher than did the response to IL-2 by lymphocytes obtained prior to IL-2 therapy. These contrasting effects on antigen-induced T cell responses vs. IL-2 induced nonspecific proliferative and cytotoxic responses suggest the importance of dose and timing of IL-2 administration when used to enhance antigen-specific T cell responses or as an immune enhancing agent combined with vaccines.
Hank
J A
JA
Department of Human Oncology, University of Wisconsin, Madison.
Sosman
J A
JA
Kohler
P C
PC
Bechhofer
R
R
Storer
B
B
Sondel
P M
PM
D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002986:Clinical Trials as Topic; D003601:Cytotoxicity Tests, Immunologic; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage / Q000009:adverse effects*; D007519:Isoantigens / Q000276:immunology; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology; D010835:Phytohemagglutinins / Q000494:pharmacology; D011994:Recombinant Proteins / Q000009:adverse effects; D013601:T-Lymphocytes / Q000187:drug effects*
D007376:Interleukin-2; D007519:Isoantigens; D010835:Phytohemagglutinins; D011994:Recombinant Proteins