Abstract
Previous work documented the capacity of dendritic cells (DC) to stimulate primary immune responses and to physically cluster with the responding lymphocytes. Rapid cell-cell aggregation assays were used here to study the interaction of DC and other types of APC with T lymphocytes. Graded doses of APC were sedimented with T cells that had been primed to alloantigens, soluble proteins, or lectin, and then labeled with carboxyfluorescein diacetate. The number of clustered T cells was measured after 10 min at 4 or 37 degrees C. At 4 degrees, binding was antigen-dependent and included greater than 50% of the added T cells. Clustering was mediated by all types of APC tested, including DC, macrophages, B lymphocytes, and fresh Langerhans cells, although DC were the most effective. Specificity was evident in the findings that alloreactive T lymphoblasts bound to allogeneic but not syngeneic APC; KLH- and OVA-reactive T cells bound to syngeneic APC in the presence of specific protein: and Con A blasts needed lectin to cluster. A 30 min pretreatment with chloroquine, a drug known to inhibit APC activity, markedly blocked the specific binding of alloreactive and protein-specific T blasts at 4 degrees C. Since Lyt-2- alloreactive blasts should specifically recognize Ia, presentation of Ia seems to be altered by chloroquine. Binding assays at 37 degrees C gave similar results to those performed at 4 degrees C, with one exception. When DC were used as APC, striking antigen-independent clustering occurred. DC could efficiently cluster primed T cells in the absence of alloantigen, soluble protein, or lectin. We suggest that antigen-independent binding contributes to the distinctive capacity of DC to prime T cells in the afferent limb of the immune response, whereas antigen-dependent binding between other APC and sensitized lymphocytes is critical in the efferent limb.
Full Text
The Full Text of this article is available as a PDF (1.4 MB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Finnegan A., Needleman B. W., Hodes R. J. Antigen processing requirements for T cell activation: differential requirements for presentation of soluble conventional antigen vs cell surface MHC determinants. J Immunol. 1985 May;134(5):2960–2965. [PubMed] [Google Scholar]
- Green J., Jotte R. Interactions between T helper cells and dendritic cells during the rat mixed lymphocyte reaction. J Exp Med. 1985 Nov 1;162(5):1546–1560. doi: 10.1084/jem.162.5.1546. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Inaba K., Granelli-Piperno A., Steinman R. M. Dendritic cells induce T lymphocytes to release B cell-stimulating factors by an interleukin 2-dependent mechanism. J Exp Med. 1983 Dec 1;158(6):2040–2057. doi: 10.1084/jem.158.6.2040. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Inaba K., Koide S., Steinman R. M. Properties of memory T lymphocytes isolated from the mixed leukocyte reaction. Proc Natl Acad Sci U S A. 1985 Nov;82(22):7686–7690. doi: 10.1073/pnas.82.22.7686. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Inaba K., Steinman R. M. Protein-specific helper T-lymphocyte formation initiated by dendritic cells. Science. 1985 Aug 2;229(4712):475–479. doi: 10.1126/science.3160115. [DOI] [PubMed] [Google Scholar]
- Inaba K., Steinman R. M. Resting and sensitized T lymphocytes exhibit distinct stimulatory (antigen-presenting cell) requirements for growth and lymphokine release. J Exp Med. 1984 Dec 1;160(6):1717–1735. doi: 10.1084/jem.160.6.1717. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Inaba K., Steinman R. M., Van Voorhis W. C., Muramatsu S. Dendritic cells are critical accessory cells for thymus-dependent antibody responses in mouse and in man. Proc Natl Acad Sci U S A. 1983 Oct;80(19):6041–6045. doi: 10.1073/pnas.80.19.6041. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lipsky P. E., Rosenthal A. S. Macrophage-lymphocyte interaction. II. Antigen-mediated physical interactions between immune guinea pig lymph node lymphocytes and syngeneic macrophages. J Exp Med. 1975 Jan 1;141(1):138–154. doi: 10.1084/jem.141.1.138. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nowell J., Quaranta V. Chloroquine affects biosynthesis of Ia molecules by inhibiting dissociation of invariant (gamma) chains from alpha-beta dimers in B cells. J Exp Med. 1985 Oct 1;162(4):1371–1376. doi: 10.1084/jem.162.4.1371. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sant A. J., Schwartz B. D., Cullen S. E. Identification of a new component in the murine Ia molecular complex. J Exp Med. 1983 Dec 1;158(6):1979–1992. doi: 10.1084/jem.158.6.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schuler G., Steinman R. M. Murine epidermal Langerhans cells mature into potent immunostimulatory dendritic cells in vitro. J Exp Med. 1985 Mar 1;161(3):526–546. doi: 10.1084/jem.161.3.526. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schwartz A. L., Bolognesi A., Fridovich S. E. Recycling of the asialoglycoprotein receptor and the effect of lysosomotropic amines in hepatoma cells. J Cell Biol. 1984 Feb;98(2):732–738. doi: 10.1083/jcb.98.2.732. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Steinman R. M., Gutchinov B., Witmer M. D., Nussenzweig M. C. Dendritic cells are the principal stimulators of the primary mixed leukocyte reaction in mice. J Exp Med. 1983 Feb 1;157(2):613–627. doi: 10.1084/jem.157.2.613. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Werdelin O., Braendstrup O., Shevach E. M. Specific absorption of T lymphocytes committed to soluble protein antigens by incubation on antigen-pulsed macrophage monolayers. J Immunol. 1979 Oct;123(4):1755–1762. [PMC free article] [PubMed] [Google Scholar]