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Growth-promoting activity of IL-1 alpha, IL-6, and tumor necrosis factor-alpha in combination with IL-2, IL-4, or IL-7 on murine thymocytes. Differential effects on CD4/CD8 subsets and on CD3+/CD3- double-negative thymocytes.
J Immunol. 1990 Apr 15; 144(8):3039-45.JI

Abstract

Many cytokines (including IL-1, IL-2, IL-4, IL-6, and TNF-alpha) have been shown to induce thymocyte proliferation in the presence of PHA. In this report, we demonstrate that certain cytokine combinations induce thymocyte proliferation in the absence of artificial comitogens. IL-1 alpha, IL-6, and TNF-alpha enhanced the proliferation of whole unseparated thymocytes in the presence of IL-2, whereas none of them induced thymocyte proliferation alone. In contrast, of these three enhancing cytokines, only IL-6 enhanced IL-4-induced proliferation. We also separated thymocytes into four groups based on their expression of CD4 and CD8, and investigated their responses to various cytokines. The results indicate that each cytokine combination affects different thymocyte subsets; thus, IL-1 alpha enhanced the proliferation of CD4-CD8- double negative (DN) thymocytes more efficiently than IL-6 in the presence of IL-2, whereas IL-6 enhanced the responses of CD4+CD8- and CD4-CD8+ single positive (SP) thymocytes to IL-2 or IL-4 better than IL-1 alpha. TNF-alpha enhanced the proliferation of both DN and both SP subsets in the presence of IL-2 and/or IL-7. None of these combinations induced the proliferation of CD4+CD8+ double positive thymocytes. Finally, DN were separated into CD3+ and CD3- populations and their responsiveness was investigated, because recent reports strongly suggest that CD3+ DN thymocytes are a mature subset of different lineage rather than precursors of SP thymocytes. CD3+ DN proliferated in response to IL-7, TNF-alpha + IL-2, and IL-1 + IL-2. CD3- DN did not respond to IL-7 or to IL-1 + IL-2, but did respond to TNF-alpha + IL-2. Finally, we detected TNF-alpha production by a cloned line of thymic macrophages, as well as by DN adult thymocytes. These results suggest that cytokines alone are capable of potent growth stimuli for thymocytes, and indicate that different combinations of these molecules act selectively on thymocytes at different developmental stages.

Authors+Show Affiliations

DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, CA 94304.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

1969882

Citation

Suda, T, et al. "Growth-promoting Activity of IL-1 Alpha, IL-6, and Tumor Necrosis Factor-alpha in Combination With IL-2, IL-4, or IL-7 On Murine Thymocytes. Differential Effects On CD4/CD8 Subsets and On CD3+/CD3- Double-negative Thymocytes." Journal of Immunology (Baltimore, Md. : 1950), vol. 144, no. 8, 1990, pp. 3039-45.
Suda T, Murray R, Guidos C, et al. Growth-promoting activity of IL-1 alpha, IL-6, and tumor necrosis factor-alpha in combination with IL-2, IL-4, or IL-7 on murine thymocytes. Differential effects on CD4/CD8 subsets and on CD3+/CD3- double-negative thymocytes. J Immunol. 1990;144(8):3039-45.
Suda, T., Murray, R., Guidos, C., & Zlotnik, A. (1990). Growth-promoting activity of IL-1 alpha, IL-6, and tumor necrosis factor-alpha in combination with IL-2, IL-4, or IL-7 on murine thymocytes. Differential effects on CD4/CD8 subsets and on CD3+/CD3- double-negative thymocytes. Journal of Immunology (Baltimore, Md. : 1950), 144(8), 3039-45.
Suda T, et al. Growth-promoting Activity of IL-1 Alpha, IL-6, and Tumor Necrosis Factor-alpha in Combination With IL-2, IL-4, or IL-7 On Murine Thymocytes. Differential Effects On CD4/CD8 Subsets and On CD3+/CD3- Double-negative Thymocytes. J Immunol. 1990 Apr 15;144(8):3039-45. PubMed PMID: 1969882.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Growth-promoting activity of IL-1 alpha, IL-6, and tumor necrosis factor-alpha in combination with IL-2, IL-4, or IL-7 on murine thymocytes. Differential effects on CD4/CD8 subsets and on CD3+/CD3- double-negative thymocytes. AU - Suda,T, AU - Murray,R, AU - Guidos,C, AU - Zlotnik,A, PY - 1990/4/15/pubmed PY - 1990/4/15/medline PY - 1990/4/15/entrez SP - 3039 EP - 45 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 144 IS - 8 N2 - Many cytokines (including IL-1, IL-2, IL-4, IL-6, and TNF-alpha) have been shown to induce thymocyte proliferation in the presence of PHA. In this report, we demonstrate that certain cytokine combinations induce thymocyte proliferation in the absence of artificial comitogens. IL-1 alpha, IL-6, and TNF-alpha enhanced the proliferation of whole unseparated thymocytes in the presence of IL-2, whereas none of them induced thymocyte proliferation alone. In contrast, of these three enhancing cytokines, only IL-6 enhanced IL-4-induced proliferation. We also separated thymocytes into four groups based on their expression of CD4 and CD8, and investigated their responses to various cytokines. The results indicate that each cytokine combination affects different thymocyte subsets; thus, IL-1 alpha enhanced the proliferation of CD4-CD8- double negative (DN) thymocytes more efficiently than IL-6 in the presence of IL-2, whereas IL-6 enhanced the responses of CD4+CD8- and CD4-CD8+ single positive (SP) thymocytes to IL-2 or IL-4 better than IL-1 alpha. TNF-alpha enhanced the proliferation of both DN and both SP subsets in the presence of IL-2 and/or IL-7. None of these combinations induced the proliferation of CD4+CD8+ double positive thymocytes. Finally, DN were separated into CD3+ and CD3- populations and their responsiveness was investigated, because recent reports strongly suggest that CD3+ DN thymocytes are a mature subset of different lineage rather than precursors of SP thymocytes. CD3+ DN proliferated in response to IL-7, TNF-alpha + IL-2, and IL-1 + IL-2. CD3- DN did not respond to IL-7 or to IL-1 + IL-2, but did respond to TNF-alpha + IL-2. Finally, we detected TNF-alpha production by a cloned line of thymic macrophages, as well as by DN adult thymocytes. These results suggest that cytokines alone are capable of potent growth stimuli for thymocytes, and indicate that different combinations of these molecules act selectively on thymocytes at different developmental stages. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/1969882/Growth_promoting_activity_of_IL_1_alpha_IL_6_and_tumor_necrosis_factor_alpha_in_combination_with_IL_2_IL_4_or_IL_7_on_murine_thymocytes__Differential_effects_on_CD4/CD8_subsets_and_on_CD3+/CD3__double_negative_thymocytes_ L2 - https://www.jimmunol.org/lookup/pmidlookup?view=long&pmid=1969882 DB - PRIME DP - Unbound Medicine ER -