Abstract
Cytotoxic T lymphocytes (CTL) are believed to play an important role in the regression of advanced malignancies in response to adoptive immunotherapy with interleukin-2 (IL-2) and lymphokine-activated killer cells or tumor-infiltrating lymphocytes. Because the current limitations to the use of adoptive immunotherapy are the IL-2 dose-dependent toxicities and the difficulty in expanding the effector cell population, recent investigations have focused on the development of newer methods for generating CTL in vitro. IL-1 and IL-6 have been shown to synegistically promote thymocyte proliferation; however, their effect on CTL development has not been studied. We investigated the ability of these two cytokines to induce CTL development from immature thymocytes. Thymocytes from 5-week-old BALB c mice were cultured for 72 hours in the presence of Con A and recombinant IL-1, IL-6, or IL-1 plus IL-6. Cytotoxicity against 51Cr-labeled P815 target cells was then measured in the presence of submitogenic doses of PHA. Neither IL-1 nor IL-6 induced a significant number of CTL from immature thymocytes. However, these two cytokines synergistically induced maximal CTL development. The monoclonal antibody to IL-4 completely abrogated CTL development induced by IL-1 and IL-6, but antibody to the IL-2 receptor had no effect. The data suggest that IL-1 and IL-6 can provide an additional method for in vitro CTL generation in adoptive immunotherapy of advanced tumors.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 397-400 |
| Number of pages | 4 |
| Journal | Journal of Pediatric Surgery |
| Volume | 26 |
| Issue number | 4 |
| DOIs | |
| State | Published - Jan 1 1991 |
| Externally published | Yes |
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Keywords
- Adoptive immunotherapy
- cytotoxic T lymphocytes
- IL-1
- IL-6
ASJC Scopus subject areas
- Surgery
Cite this
Induction of cytotoxic T lymphocyte development from murine thymocytes by IL-1 and IL-6. / Ford, Henri; Hoffman, Rosemary A.; Wang, Stewart; Simmons, Richard L.
In: Journal of Pediatric Surgery, Vol. 26, No. 4, 01.01.1991, p. 397-400.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Induction of cytotoxic T lymphocyte development from murine thymocytes by IL-1 and IL-6
AU - Ford, Henri
AU - Hoffman, Rosemary A.
AU - Wang, Stewart
AU - Simmons, Richard L.
PY - 1991/1/1
Y1 - 1991/1/1
N2 - Cytotoxic T lymphocytes (CTL) are believed to play an important role in the regression of advanced malignancies in response to adoptive immunotherapy with interleukin-2 (IL-2) and lymphokine-activated killer cells or tumor-infiltrating lymphocytes. Because the current limitations to the use of adoptive immunotherapy are the IL-2 dose-dependent toxicities and the difficulty in expanding the effector cell population, recent investigations have focused on the development of newer methods for generating CTL in vitro. IL-1 and IL-6 have been shown to synegistically promote thymocyte proliferation; however, their effect on CTL development has not been studied. We investigated the ability of these two cytokines to induce CTL development from immature thymocytes. Thymocytes from 5-week-old BALB c mice were cultured for 72 hours in the presence of Con A and recombinant IL-1, IL-6, or IL-1 plus IL-6. Cytotoxicity against 51Cr-labeled P815 target cells was then measured in the presence of submitogenic doses of PHA. Neither IL-1 nor IL-6 induced a significant number of CTL from immature thymocytes. However, these two cytokines synergistically induced maximal CTL development. The monoclonal antibody to IL-4 completely abrogated CTL development induced by IL-1 and IL-6, but antibody to the IL-2 receptor had no effect. The data suggest that IL-1 and IL-6 can provide an additional method for in vitro CTL generation in adoptive immunotherapy of advanced tumors.
AB - Cytotoxic T lymphocytes (CTL) are believed to play an important role in the regression of advanced malignancies in response to adoptive immunotherapy with interleukin-2 (IL-2) and lymphokine-activated killer cells or tumor-infiltrating lymphocytes. Because the current limitations to the use of adoptive immunotherapy are the IL-2 dose-dependent toxicities and the difficulty in expanding the effector cell population, recent investigations have focused on the development of newer methods for generating CTL in vitro. IL-1 and IL-6 have been shown to synegistically promote thymocyte proliferation; however, their effect on CTL development has not been studied. We investigated the ability of these two cytokines to induce CTL development from immature thymocytes. Thymocytes from 5-week-old BALB c mice were cultured for 72 hours in the presence of Con A and recombinant IL-1, IL-6, or IL-1 plus IL-6. Cytotoxicity against 51Cr-labeled P815 target cells was then measured in the presence of submitogenic doses of PHA. Neither IL-1 nor IL-6 induced a significant number of CTL from immature thymocytes. However, these two cytokines synergistically induced maximal CTL development. The monoclonal antibody to IL-4 completely abrogated CTL development induced by IL-1 and IL-6, but antibody to the IL-2 receptor had no effect. The data suggest that IL-1 and IL-6 can provide an additional method for in vitro CTL generation in adoptive immunotherapy of advanced tumors.
KW - Adoptive immunotherapy
KW - cytotoxic T lymphocytes
KW - IL-1
KW - IL-6
UR - http://www.scopus.com/inward/record.url?scp=0025892627&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0025892627&partnerID=8YFLogxK
U2 - 10.1016/0022-3468(91)90985-3
DO - 10.1016/0022-3468(91)90985-3
M3 - Article
C2 - 2056398
AN - SCOPUS:0025892627
VL - 26
SP - 397
EP - 400
JO - Journal of Pediatric Surgery
JF - Journal of Pediatric Surgery
SN - 0022-3468
IS - 4
ER -