Abstract
Experiments were designed to discover whether locomotor or chemotactic events are needed for clustering of lymphocytes with accessory cells or, conversely, whether clustering precedes the activation of lymphocyte locomotion. The time-courses of clustering and locomotor activation were compared and the behaviour of moving cells during cluster formation was filmed. Human lymphocytes direct from blood were activated by culture for 24-48 hr with anti-CD3 antibody or in allogeneic mixed leucocyte reactions (AMLR). The proportion of clustered and locomotor lymphocytes was low at the beginning of culture. Clusters appeared during the first few hours, before the increase in numbers of locomotor lymphocytes. Filming gave no evidence that the cells attracted one another chemotactically to form clusters. Rather, cells made chance contact by random locomotion and then remained adherent, though lymphocytes very close (less than or equal to 10 microns) to clusters did show increased pseudopod formation towards the cluster. However, the behaviour of motile lymphocytes responding to monocytes or macrophages given a phagocytic stimulus was different. Human monocytes which ingested opsonized zymosan released a material during but not following phagocytosis which caused an immediate increase in polar shape-change in lymphocytes. Macrophages from Corynebacterium parvum-induced mouse peritoneal exudates, given a phagocytic stimulus (opsonized Candida albicans), acted as sources of chemotactic gradients which attracted nearby lymphocytes to form clusters. This was due to brief release of a material immediately following phagocytosis, but after 15 min or so the macrophages no longer attracted nearby cells. These experiments suggest that, during induction of an immune response to a non-phagocytic stimulus, clusters form slowly by random contact followed by preferential adhesion. However, after phagocytosis, there may be a chemotactic response to the ingesting macrophage. This may help to focus lymphocytes onto macrophages which present microbial antigens.
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Selected References
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- Allan R. B., Wilkinson P. C. A visual analysis of chemotactic and chemokinetic locomotion of human neutrophil leucocytes. Use of a new chemotaxis assay with Candida albicans as gradient source. Exp Cell Res. 1978 Jan;111(1):191–203. doi: 10.1016/0014-4827(78)90249-5. [DOI] [PubMed] [Google Scholar]
- Austyn J. M. Lymphoid dendritic cells. Immunology. 1987 Oct;62(2):161–170. [PMC free article] [PubMed] [Google Scholar]
- Berman L. Lymphocytes and macrophages in vitro. Their activties in relation to functions of small lymphocytes. Lab Invest. 1966 Jun;15(6):1084–1099. [PubMed] [Google Scholar]
- Biberfeld P. Uropod formation in phytohaemagglutinin (PHA) stimulated lymphocytes. Exp Cell Res. 1971 Jun;66(2):433–445. doi: 10.1016/0014-4827(71)90698-7. [DOI] [PubMed] [Google Scholar]
- El-Naggar A., Van Epps D. E., Williams R. C., Jr Effect of culturing on the human lymphocyte locomotion response to casein, C5a, and fMet-Leu-Phe. Cell Immunol. 1981 May 1;60(1):43–49. doi: 10.1016/0008-8749(81)90246-x. [DOI] [PubMed] [Google Scholar]
- Haston W. S., Wilkinson P. C. Visual methods for measuring leukocyte locomotion. Methods Enzymol. 1988;162:17–38. doi: 10.1016/0076-6879(88)62060-x. [DOI] [PubMed] [Google Scholar]
- Larsen C. G., Anderson A. O., Appella E., Oppenheim J. J., Matsushima K. The neutrophil-activating protein (NAP-1) is also chemotactic for T lymphocytes. Science. 1989 Mar 17;243(4897):1464–1466. doi: 10.1126/science.2648569. [DOI] [PubMed] [Google Scholar]
- Lipsky P. E., Rosenthal A. S. Macrophage-lymphocyte interaction. I. Characteristics of the antigen-independent-binding of guinea pig thymocytes and lymphocytes to syngeneic macrophages. J Exp Med. 1973 Oct 1;138(4):900–924. doi: 10.1084/jem.138.4.900. [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]
- MCFARLAND W., HEILMAN D. H. LYMPHOCYTE FOOT APPENDAGE: ITS ROLE IN LYMPHOCYTE FUNCTION AND IN IMMUNOLOGICAL REACTIONS. Nature. 1965 Feb 27;205:887–888. doi: 10.1038/205887a0. [DOI] [PubMed] [Google Scholar]
- McFarland W., Heilman D. H., Moorhead J. F. Functional anatomy of the lymphocyte in immunological reactions in vitro. J Exp Med. 1966 Nov 1;124(5):851–858. doi: 10.1084/jem.124.5.851. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McFarland W., Schechter G. P. The lymphocyte in immunological reactions in vitro: ultrastructural studies. Blood. 1970 May;35(5):683–688. [PubMed] [Google Scholar]
- McGregor D. D., Logie P. S. The mediator of cellular immunity. VII. Localization of sensitized lymphocytes in inflammatory exudates. J Exp Med. 1974 Jun 1;139(6):1415–1430. doi: 10.1084/jem.139.6.1415. [DOI] [PMC free article] [PubMed] [Google Scholar]
- O'Neill G. J., Parrott D. M. Locomotion of human lymphoid cells. I. Effect of culture and con A on T and non-T lymphocytes. Cell Immunol. 1977 Oct;33(2):257–267. doi: 10.1016/0008-8749(77)90156-3. [DOI] [PubMed] [Google Scholar]
- Petri J., Braendstrup O., Werdelin O. Macrophage-lymphocyte clusters in the immune response to soluble protein antigen in vitro. VIII. Cinephotomicrographic studies. Scand J Immunol. 1979;10(6):493–498. doi: 10.1111/j.1365-3083.1979.tb01380.x. [DOI] [PubMed] [Google Scholar]
- Potter J. W., Van Epps D. E. Human T-lymphocyte chemotactic activity: nature and production in response to antigen. Cell Immunol. 1986 Jan;97(1):59–66. doi: 10.1016/0008-8749(86)90375-8. [DOI] [PubMed] [Google Scholar]
- Steinman R. M., Witmer M. D. Lymphoid dendritic cells are potent stimulators of the primary mixed leukocyte reaction in mice. Proc Natl Acad Sci U S A. 1978 Oct;75(10):5132–5136. doi: 10.1073/pnas.75.10.5132. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wilkinson P. C., Higgins A. Cyclosporin A inhibits mitogen-activated but not phorbol ester-activated locomotion of human lymphocytes. Immunology. 1987 Jul;61(3):311–316. [PMC free article] [PubMed] [Google Scholar]
- Wilkinson P. C., Higgins A. OKT3-activated locomotion of human blood lymphocytes: a phenomenon requiring contact of T cells with Fc receptor-bearing cells. Immunology. 1987 Mar;60(3):445–451. [PMC free article] [PubMed] [Google Scholar]
- Wilkinson P. C., Islam L. N. Recombinant IL-4 and IFN-gamma activate locomotor capacity in human B lymphocytes. Immunology. 1989 Jun;67(2):237–243. [PMC free article] [PubMed] [Google Scholar]
- Wilkinson P. C. The locomotor capacity of human lymphocytes and its enhancement by cell growth. Immunology. 1986 Feb;57(2):281–289. [PMC free article] [PubMed] [Google Scholar]
- Wilkinson P. C. Visual observations of chemotaxis and chemotropism in mouse macrophages. Immunobiology. 1982 Apr;161(3-4):376–384. doi: 10.1016/S0171-2985(82)80095-8. [DOI] [PubMed] [Google Scholar]
- Yoshimura T., Matsushima K., Tanaka S., Robinson E. A., Appella E., Oppenheim J. J., Leonard E. J. Purification of a human monocyte-derived neutrophil chemotactic factor that has peptide sequence similarity to other host defense cytokines. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9233–9237. doi: 10.1073/pnas.84.24.9233. [DOI] [PMC free article] [PubMed] [Google Scholar]