Abstract
Antigen-primed T cells have been shown to require I-region-compatible adherent cells, as well as the priming antigen, to proliferate in vitro. We postulated that the Ia-recognition event is required for the T cell to induce secretion of the monokine interleukin 1 (IL 1) from adherent cells; the conventionally held view is that Ia is directly required for T cell activation. Our hypothesis predicts that IL I could replace the requirement for Ia+ cells in T cell proliferation assays in vitro. To test this prediction, we depleted keyhole limpet hemocyanin (KLH)-primed C57BL/6 mouse lymph node cells of I-A+ cells by treating with monoclonal anti-I-Ab and complement. As expected, this treatment eliminated the ability of KLH to provoke a proliferative response by primed T cells. Proliferation was restored by providing exogenous IL 1, but only in conjunction with added KLH. The proliferative response of primed T cells could also be blocked by adding anti-I-Ab to culture, and this inhibition could similarly be reversed by providing IL 1 in the presence of the specific antigen KLH. On the basis of these findings we propose a model of T cell activation and discuss its implications.
MeSH Terms
Animals
Antigens
Histocompatibility Antigens Class II/immunology
Immunologic Memory
Interleukin-1/immunology,pharmacology
Lymphocyte Activation/drug effects
Male
Mice
Mice, Inbred C57BL
Models, Biological
T-Lymphocytes/immunology
Chemicals
Antigens
Histocompatibility Antigens Class II
Interleukin-1
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Durum S K
Gershon R K
References (26)
26 references, click to expand
-
Studies on the purification and structure-functional relationships of murine lymphocyte activating factor (Interleukin 1).
Mol Immunol. 1980 May;17(5):571-7
PMID: 6971397
-
The function of macrophages in antigen recognition by guinea pig T lymphocytes. III. Genetic analysis of the antigens mediating macrophage-T lymphocyte interaction.
J Immunol. 1976 May;116(5):1482-9
PMID: 1083875
-
Requirement for an Ia-bearing accessory cell in Con A-induced T cell proliferation.
J Immunol. 1978 Nov;121(5):1981-9
PMID: 81859
-
Cellular origins of co-stimulator (IL2) and its activity in cytotoxic T lymphocyte responses.
J Immunol. 1980 May;124(5):2231-9
PMID: 6965968
-
A THREE-CELL INTERACTION REQUIRED FOR THE INDUCTION OF THE PRIMARY IMMUNE RESPONSE in vitro.
Proc Natl Acad Sci U S A. 1968 Oct;61(2):542-7
PMID: 16591704
-
Studies on the role of lymphocyte-activating factor (Interleukin 1) in antigen-induced lymph node lymphocyte proliferation.
Cell Immunol. 1980 Sep 1;54(2):382-9
PMID: 6774815
-
On the thymus in the differentiation of "H-2 self-recognition" by T cells: evidence for dual recognition?
J Exp Med. 1978 Mar 1;147(3):882-96
PMID: 305459
-
Two distinct factors are required for induction of T-cell growth.
Nature. 1980 Feb 14;283(5748):664-6
PMID: 6965520
-
The role of macrophages in the activation of T lymphocytes by concanavalin A. III. Macrophage-independent activation.
Eur J Immunol. 1981 Feb;11(2):120-6
PMID: 6163640
-
Preparation of lymphocyte-activating factor from continuous murine macrophage cell lines.
Cell Immunol. 1977 Dec;34(2):416-9
PMID: 563294
-
Mechanisms of action of 'lymphocyte activating factor' (LAF) I. Association of lymphocyte activating factor action with early DNA synthesis in PHA-stimulated lymphocytes.
Immunology. 1977 Nov;33(5):663-9
PMID: 590994
-
Lymphocyte specificity to protein antigens. I. Characterization of the antigen-induced in vitro T cell-dependent proliferative response with lymph node cells from primed mice.
J Immunol. 1977 Sep;119(3):1048-53
PMID: 70468
-
Cell-cell interactions in the T cell proliferative response. I. Analysis of the cell types involved and evidence for nonspecific T cell recruitment.
J Immunol. 1980 Aug;125(2):491-500
PMID: 6771325
-
Studies on the mechanism of fever accompanying delayed hypersensitivity. The role of the sensitized lymphocyte.
J Exp Med. 1972 May 1;135(5):1113-32
PMID: 4112261
-
Role of Ia-positive cells in the production of T cell-replacing factors: blocking of factor production with anti-Ia serum.
J Immunol. 1980 Sep;125(3):1224-9
PMID: 6967893
-
Secretion of mediators following T lymphocyte-macrophage interaction is regulated by the major histocompatibility complex.
Proc Natl Acad Sci U S A. 1977 Aug;74(8):3542-6
PMID: 410022
-
Self recognition in allogeneic radiation bone marrow chimeras. A radiation-resistant host element dictates the self specificity and immune response gene phenotype of T-helper cells.
J Exp Med. 1981 May 1;153(5):1286-301
PMID: 6166716
-
Antigen-specific stimulation and trans-stimulation of T cells in long-term culture.
Eur J Immunol. 1979 Sep;9(9):665-70
PMID: 92410
-
Function of macrophages in antigen recognition by guinea pig T lymphocytes. I. Requirement for histocompatible macrophages and lymphocytes.
J Exp Med. 1973 Nov 1;138(5):1194-212
PMID: 4542806
-
Activation of T lymphocytes by lectins and carbohydrate-oxidizing reagents viewed as an immunological recognition of cell-surface modifications seen in the context of "self" major histocompatibility complex antigens.
Eur J Immunol. 1981 Jun;11(6):475-83
PMID: 6266838
-
How T lymphocytes recognize antigen.
Crit Rev Immunol. 1980 May;1(2):133-64
PMID: 6174271
-
T-T cell interactions during cytotoxic T lymphocyte (CTL) responses: T cell derived helper factor (Interleukin 2) as a probe to analyze CTL responsiveness and thymic maturation of CTL progenitors.
Immunol Rev. 1980;51:215-55
PMID: 7000672
-
Potentiation of cultured mouse thymocyte responses by factors released by peripheral leucocytes.
J Immunol. 1971 Dec;107(6):1778-80
PMID: 4941117
-
Monoclonal antibodies to guinea pig Ia antigens. II. Effect on alloantigen-, antigen-, and mitogen-induced T lymphocyte proliferation in vitro.
J Exp Med. 1980 Oct 1;152(4):1011-23
PMID: 6158543
-
Effects of anti-Ia serum on mitogenic responses. I. Inhibition of the proliferative response to B cell mitogen, LPS, by specific anti-Ia sera.
J Immunol. 1975 Dec;115(6):1672-6
PMID: 1081105
-
A one-receptor view of T-cell behaviour.
Nature. 1981 Aug 6;292(5823):497-501
PMID: 6166871