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. 1983 Oct 1;158(4):1227–1242. doi: 10.1084/jem.158.4.1227

Immune cell populations in cutaneous delayed-type hypersensitivity

PMCID: PMC2187374  PMID: 6604784

Abstract

Delayed-type hypersensitivity (DTH) is a prototypic T lymphocyte- mediated response to antigenic challenge. In this study, mononuclear cells infiltrating the skin during cutaneous response to tuberculin in presensitized human subjects (responders) and nonimmune controls were identified using monoclonal antibodies by indirect immunofluorescence. In both responders and controls the infiltrate consisted mainly of T lymphocytes (T11+ and OKT3+) and monocytes (OKM1+, 63D3+, Mo2+) which initially accumulated in proximity to small blood vessels and later infiltrated the interstitial dermis and epidermis. More T lymphocytes reacted with OKT4 than with OKT8. 6 h after tuberculin the ratio of OKT4/OKT8 in tissue from responders exceeded that in blood, whereas in tissues studied at 15-48 h and in all control tissues those ratios in blood and tissue were similar. Evidence of T lymphocyte activation was sought using monoclonal antibodies anti-Tac, OKT9, and OKT10. In responders but not in controls the proportion of infiltrating cells reactive with these antibodies increased during the course of DTH. The presence of activated T lymphocytes in tissue was not associated with a comparable increase in peripheral blood cell populations identified by anti-Tac and OKT10. Studies using anti-B1, Leu-7, and anti-IgD/IgM revealed comparatively few reactive cells. Dual-labeling studies demonstrated that most Leu-7--reactive cells also bound T11 while fewer bound OKM1 or OKT8 and that cells reactive with OKIa1 and T11 constituted largely nonoverlapping populations. Specific patterns of reactivity were not observed when tissues were stained with anti-human C3, or poly C9-MA, a monoclonal antibody reactive with a neoantigen on polymerized C9 of the membrane attack complex of complement. The number of epidermal Langerhans cells identified by OKT6 was similar in responders and controls. Thus, the cutaneous response to tuberculin in sensitized individuals is characterized by early enrichment of the OKT4 subpopulation of T lymphocytes in tissue infiltrates and subsequent (15- 48 h) evidence of T lymphocyte activation.

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Selected References

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  1. Abo T., Cooper M. D., Balch C. M. Characterization of HNK-1+ (Leu-7) human lymphocytes. I. Two distinct phenotypes of human NK cells with different cytotoxic capability. J Immunol. 1982 Oct;129(4):1752–1757. [PubMed] [Google Scholar]
  2. BILLINGHAM R. E., BRENT L., MEDAWAR P. B. Quantitative studies on tissue transplantation immunity. II. The origin, strength and duration of actively and adoptively acquired immunity. Proc R Soc Lond B Biol Sci. 1954 Dec 15;143(910):58–80. doi: 10.1098/rspb.1954.0054. [DOI] [PubMed] [Google Scholar]
  3. BRENT L., BROWN J., MEDAWAR P. B. Skin transplantation immunity in relation to hypersensitivity. Lancet. 1958 Sep 13;2(7046):561–564. doi: 10.1016/s0140-6736(58)90202-2. [DOI] [PubMed] [Google Scholar]
  4. Bhan A. K., Mihm M. C., Jr, Dvorak H. F. T cell subsets in allograft rejection. In situ characterization of T cell subsets in human skin allografts by the use of monoclonal antibodies. J Immunol. 1982 Oct;129(4):1578–1583. [PubMed] [Google Scholar]
  5. Bhan A. K., Nadler L. M., Stashenko P., McCluskey R. T., Schlossman S. F. Stages of B cell differentiation in human lymphoid tissue. J Exp Med. 1981 Sep 1;154(3):737–749. doi: 10.1084/jem.154.3.737. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bhan A. K., Reinherz E. L., Poppema S., McCluskey R. T., Schlossman S. F. Location of T cell and major histocompatibility complex antigens in the human thymus. J Exp Med. 1980 Oct 1;152(4):771–782. doi: 10.1084/jem.152.4.771. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cotner T., Williams J. M., Christenson L., Shapiro H. M., Strom T. B., Strominger J. Simultaneous flow cytometric analysis of human T cell activation antigen expression and DNA content. J Exp Med. 1983 Feb 1;157(2):461–472. doi: 10.1084/jem.157.2.461. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dallman M. J., Mason D. W. Role of thymus-derived and thymus-independent cells in murine skin allograft rejection. Transplantation. 1982 Mar;33(3):221–223. doi: 10.1097/00007890-198203000-00002. [DOI] [PubMed] [Google Scholar]
  9. Dennert G., Weiss S., Warner J. F. T cells may express multiple activities: specific allohelp, cytolysis, and delayed-type hypersensitivity are expressed by a cloned T-cell line. Proc Natl Acad Sci U S A. 1981 Jul;78(7):4540–4543. doi: 10.1073/pnas.78.7.4540. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Dvorak H. F., Mihm M. C., Jr, Dvorak A. M., Johnson R. A., Manseau E. J., Morgan E., Colvin R. B. Morphology of delayed type hypersensitivity reactions in man. I. Quantitative description of the inflammatory response. Lab Invest. 1974 Aug;31(2):111–130. [PubMed] [Google Scholar]
  11. Fauser A. A., Messner H. A. Granuloerythropoietic colonies in human bone marrow, peripheral blood, and cord blood. Blood. 1978 Dec;52(6):1243–1248. [PubMed] [Google Scholar]
  12. Godfrey H. P., Gell P. G. Cellular and molecular events in the delayed-onset hypersensitivities. Rev Physiol Biochem Pharmacol. 1978;84:1–92. doi: 10.1007/BFb0030490. [DOI] [PubMed] [Google Scholar]
  13. Hercend T., Ritz J., Schlossman S. F., Reinherz E. L. Comparative expression of T9, T10, and Ia antigens on activated human T cell subsets. Hum Immunol. 1981 Nov;3(3):247–259. doi: 10.1016/0198-8859(81)90021-5. [DOI] [PubMed] [Google Scholar]
  14. Hill W. C. The influence of the cellular infiltrate on the evolution and intensity of delayed hypersensitivity reactions. J Exp Med. 1969 Feb 1;129(2):363–370. doi: 10.1084/jem.129.2.363. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Huber B., Devinsky O., Gershon R. K., Cantor H. Cell-mediated immunity: delayed-type hypersensitivity and cytotoxic responses are mediated by different T-cell subclasses. J Exp Med. 1976 Jun 1;143(6):1534–1539. doi: 10.1084/jem.143.6.1534. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hunninghake G. W., Crystal R. G. Pulmonary sarcoidosis: a disorder mediated by excess helper T-lymphocyte activity at sites of disease activity. N Engl J Med. 1981 Aug 20;305(8):429–434. doi: 10.1056/NEJM198108203050804. [DOI] [PubMed] [Google Scholar]
  17. Lampert I. A., Janossy G., Suitters A. J., Bofill M., Palmer S., Gordon-Smith E., Prentice H. G., Thomas J. A. Immunological analysis of the skin in graft versus host disease. Clin Exp Immunol. 1982 Oct;50(1):123–131. [PMC free article] [PubMed] [Google Scholar]
  18. Leung K. N., Ada G. L. Two T-cell populations mediate delayed-type hypersensitivity to murine influenza virus infection. Scand J Immunol. 1980;12(6):481–487. doi: 10.1111/j.1365-3083.1980.tb00094.x. [DOI] [PubMed] [Google Scholar]
  19. Lin Y. L., Askonas B. A. Biological properties of an influenza A virus-specific killer T cell clone. Inhibition of virus replication in vivo and induction of delayed-type hypersensitivity reactions. J Exp Med. 1981 Aug 1;154(2):225–234. doi: 10.1084/jem.154.2.225. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Loveland B. E., McKenzie I. F. Which T cells cause graft rejection? Transplantation. 1982 Mar;33(3):217–221. doi: 10.1097/00007890-198203000-00001. [DOI] [PubMed] [Google Scholar]
  21. MITCHISON N. A. Passive transfer of transplantation immunity. Proc R Soc Lond B Biol Sci. 1954 Feb 18;142(906):72–87. doi: 10.1098/rspb.1954.0007. [DOI] [PubMed] [Google Scholar]
  22. Mackaness G. B. The influence of immunologically committed lymphoid cells on macrophage activity in vivo. J Exp Med. 1969 May 1;129(5):973–992. doi: 10.1084/jem.129.5.973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Marchal G., Seman M., Milon G., Truffa-Bachi P., Zilberfarb V. Local adoptive transfer of skin delayed-type hypersensitivity initiated by a single T lymphocyte. J Immunol. 1982 Sep;129(3):954–958. [PubMed] [Google Scholar]
  24. Meuer S. C., Schlossman S. F., Reinherz E. L. Clonal analysis of human cytotoxic T lymphocytes: T4+ and T8+ effector T cells recognize products of different major histocompatibility complex regions. Proc Natl Acad Sci U S A. 1982 Jul;79(14):4395–4399. doi: 10.1073/pnas.79.14.4395. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Michael A. F., Yang J. Y., Falk R. J., Bennington M. J., Scheinman J. I., Vernier R. L., Fish A. J. Monoclonal antibodies to human renal basement membranes: heterogenic and ontogenic changes. Kidney Int. 1983 Jul;24(1):74–86. doi: 10.1038/ki.1983.128. [DOI] [PubMed] [Google Scholar]
  26. Milon G., Marchal G., Seman M., Truffa-Bachi P., Zilberfarb V. Is the delayed-type hypersensitivity observed after a low dose of antigen mediated by helper T cells? J Immunol. 1983 Mar;130(3):1103–1107. [PubMed] [Google Scholar]
  27. Murphy G. F., Bhan A. K., Sato S., Harrist T. J., Mihm M. C., Jr Characterization of Langerhans cells by the use of monoclonal antibodies. Lab Invest. 1981 Nov;45(5):465–468. [PubMed] [Google Scholar]
  28. NAJARIAN J. S., FELDMAN J. D. SPECIFICITY OF PASSIVELY TRANSFERRED DELAYED HYPERSENSITIVITY. J Exp Med. 1963 Sep 1;118:341–352. doi: 10.1084/jem.118.3.341. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Okudaira K., Goodwin J. S., Williams R. C., Jr Anti-Ia antibody in the sera of normal subjects after in vivo antigenic stimulation. J Exp Med. 1982 Jul 1;156(1):255–267. doi: 10.1084/jem.156.1.255. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. PATERSON P. Y. Transfer of allergic encephalomyelitis in rats by means of lymph node cells. J Exp Med. 1960 Jan 1;111:119–136. doi: 10.1084/jem.111.1.119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Platt J. L., LeBien T. W., Michael A. F. Interstitial mononuclear cell populations in renal graft rejection. Identification by monoclonal antibodies in tissue sections. J Exp Med. 1982 Jan 1;155(1):17–30. doi: 10.1084/jem.155.1.17. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Platt J. L., Michael A. F. Retardation of fading and enhancement of intensity of immunofluorescence by p-phenylenediamine. J Histochem Cytochem. 1983 Jun;31(6):840–842. doi: 10.1177/31.6.6341464. [DOI] [PubMed] [Google Scholar]
  33. Poppema S., Bhan A. K., Reinherz E. L., McCluskey R. T., Schlossman S. F. Distribution of T cell subsets in human lymph nodes. J Exp Med. 1981 Jan 1;153(1):30–41. doi: 10.1084/jem.153.1.30. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Poulter L. W., Seymour G. J., Duke O., Janossy G., Panayi G. Immunohistological analysis of delayed-type hypersensitivity in man. Cell Immunol. 1982 Dec;74(2):358–369. doi: 10.1016/0008-8749(82)90036-3. [DOI] [PubMed] [Google Scholar]
  35. Reinherz E. L., Kung P. C., Goldstein G., Levey R. H., Schlossman S. F. Discrete stages of human intrathymic differentiation: analysis of normal thymocytes and leukemic lymphoblasts of T-cell lineage. Proc Natl Acad Sci U S A. 1980 Mar;77(3):1588–1592. doi: 10.1073/pnas.77.3.1588. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Reinherz E. L., Schlossman S. F. The differentiation and function of human T lymphocytes. Cell. 1980 Apr;19(4):821–827. doi: 10.1016/0092-8674(80)90072-0. [DOI] [PubMed] [Google Scholar]
  37. Ritchie A. W., James K., Micklem H. S. The distribution and possible significance of cells identified in human lymphoid tissue by the monoclonal antibody HNK-1. Clin Exp Immunol. 1983 Mar;51(3):439–447. [PMC free article] [PubMed] [Google Scholar]
  38. Scheynius A., Klareskog L., Forsum U. In situ identification of T lymphocyte subsets and HLA-DR expressing cells in the human skin tuberculin reaction. Clin Exp Immunol. 1982 Aug;49(2):325–330. [PMC free article] [PubMed] [Google Scholar]
  39. Suitters A. J., Lampert I. A. Expression of Ia antigen on epidermal keratinocytes is a consequence of cellular immunity. Br J Exp Pathol. 1982 Apr;63(2):207–213. [PMC free article] [PubMed] [Google Scholar]
  40. Van Voorhis W. C., Kaplan G., Sarno E. N., Horwitz M. A., Steinman R. M., Levis W. R., Nogueira N., Hair L. S., Gattass C. R., Arrick B. A. The cutaneous infiltrates of leprosy: cellular characteristics and the predominant T-cell phenotypes. N Engl J Med. 1982 Dec 23;307(26):1593–1597. doi: 10.1056/NEJM198212233072601. [DOI] [PubMed] [Google Scholar]
  41. van Dinther-Janssen A. C., van Maarsseveen A. C., de Groot J., Scheper R. J. Comparative migration of T- and B-lymphocyte subpopulations into skin inflammatory sites. Immunology. 1983 Mar;48(3):519–527. [PMC free article] [PubMed] [Google Scholar]

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