Abstract
Thymus-derived lymphocyte (T-cell) function, as determined in vivo by cutaneous reactivity to several antigens and in vitro by responsiveness to mitogens and antigens, was assessed in 14 patients infected with a variety of fungal organisms. While all patients manifested a normal frequency of peripheral blood T cells, only seven patients reacted to at least one of the antigens used for cutaneous testing and demonstrated normal in vitro T proliferative responses. Three patients exhibited cutaneous anergy but normal in vitro T-cell reactivity while four patients demonstrated persistent anergy and marked in vitro T-cell hyporeactivity which was independent of activity of infection, concurrent medication, or any associated disorders. The marked diminution of in vitro T-cell reactivity noted for these later four patients was not due to a deletion of antigen- or mitogen-reactive cells. Thus, patients' cells which had been initially cultured for 7 days without any mitogenic or antigenic stimulus and which were subsequently washed and recultured with phytohemagglutinin, concanavalin A, or histoplasmin demonstrated a marked increase in their responsiveness. Moreover, this reactivity noted for recultured cells could be suppressed by a nonphagocytic, nonadherent, nonimmunoglobulin-bearing, sheep red blood cell rosette-forming population of cells isolated from the fresh peripheral blood mononuclear cells of the same patient. While these "regulator" T cells were capable of suppressing T-proliferative responses to antigens and mitogens, they did not diminish pokeweed mitogen-induced immunoglobulin synthesis by normal bone marrow-derived lymphocytes. Patients in whom suppressor "T" cells were found were at risk for relapsing, disseminated fungal infection.
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Selected References
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- Alford R. H., Goodwin R. A. Variation in lymphocyte reactivity to histoplasmin during the course of chronic pulmonary histoplasmosis. Am Rev Respir Dis. 1973 Jul;108(1):85–92. doi: 10.1164/arrd.1973.108.1.85. [DOI] [PubMed] [Google Scholar]
- Biggar W. D., Meuwissen H. J., Good R. A. Successful defense against Histoplasma capsulatum in hypogammaglobulinemia. Arch Intern Med. 1971 Oct;128(4):585–587. [PubMed] [Google Scholar]
- Boyle W. An extension of the 51Cr-release assay for the estimation of mouse cytotoxins. Transplantation. 1968 Sep;6(6):761–764. doi: 10.1097/00007890-196809000-00002. [DOI] [PubMed] [Google Scholar]
- Catanzaro A., Spitler L., Moser K. M. Immunotherapy of coccidioidomycosis. J Clin Invest. 1974 Sep;54(3):690–701. doi: 10.1172/JCI107807. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Claman H. N., Chaperon E. A. Immunologic complementation between thymus and marrow cells--a model for the two-cell theory of immunocompetence. Transplant Rev. 1969;1:92–113. doi: 10.1111/j.1600-065x.1969.tb00137.x. [DOI] [PubMed] [Google Scholar]
- Contractor S. F., Davies H. Effect of human chorionic somatomammotrophin and human chorionic gonadotrophin on phytohaemagglutinin-induced lymphocyte transformation. Nat New Biol. 1973 Jun 27;243(130):284–286. doi: 10.1038/newbio243284a0. [DOI] [PubMed] [Google Scholar]
- Diamond R. D., Bennett J. E. Disseminated cryptococcosis in man: decreased lymphocyte transformation in response to Cryptococcus neoformans. J Infect Dis. 1973 Jun;127(6):694–697. doi: 10.1093/infdis/127.6.694. [DOI] [PubMed] [Google Scholar]
- Gershon R. K. T cell control of antibody production. Contemp Top Immunobiol. 1974;3:1–40. doi: 10.1007/978-1-4684-3045-5_1. [DOI] [PubMed] [Google Scholar]
- Graybill J. R., Alford R. H. Cell-mediated immunity in Cryptococcosis. Cell Immunol. 1974 Oct;14(1):12–21. doi: 10.1016/0008-8749(74)90164-6. [DOI] [PubMed] [Google Scholar]
- Ha T. Y., Waksman B. H. Role of the thymus in tolerance. X. "Suppressor" activity of antigen-stimulated rat thymocytes transferred to normal recipients. J Immunol. 1973 May;110(5):1290–1299. [PubMed] [Google Scholar]
- Horiuchi A., Waksman B. H. Role of the thymus in tolerance. 8. Relative effectiveness of nonaggregated and heat-aggregated bovine gamma globulin, injected directly into lymphoid organs of normal rats, in suppressing immune responsiveness. J Immunol. 1968 Dec;101(6):1322–1332. [PubMed] [Google Scholar]
- Jondal M., Holm G., Wigzell H. Surface markers on human T and B lymphocytes. I. A large population of lymphocytes forming nonimmune rosettes with sheep red blood cells. J Exp Med. 1972 Aug 1;136(2):207–215. doi: 10.1084/jem.136.2.207. [DOI] [PMC free article] [PubMed] [Google Scholar]
- KAMRIN B. B. Successful skin bomografts in mature non-littermate rats treated with fractions containing alpha-globulins. Proc Soc Exp Biol Med. 1959 Jan;100(1):58–61. doi: 10.3181/00379727-100-24522. [DOI] [PubMed] [Google Scholar]
- Katz D. H., Benacerraf B. The regulatory influence of activated T cells on B cell responses to antigen. Adv Immunol. 1972;15:1–94. doi: 10.1016/s0065-2776(08)60683-5. [DOI] [PubMed] [Google Scholar]
- Kirchner H., Chused T. M., Herberman R. B., Holden H. T., Lavrin D. H. Evidence of suppressor cell activity in spleens of mice bearing primary tumors induced by Moloney sarcoma virus. J Exp Med. 1974 Jun 1;139(6):1473–1487. doi: 10.1084/jem.139.6.1473. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kirkpatrick C. H., Rich R. R., Bennett J. E. Chronic mucocutaneous candidiasis: model-building in cellular immunity. Ann Intern Med. 1971 Jun;74(6):955–978. doi: 10.7326/0003-4819-74-6-955. [DOI] [PubMed] [Google Scholar]
- Li C. Y., Lam K. W., Yam L. T. Esterases in human leukocytes. J Histochem Cytochem. 1973 Jan;21(1):1–12. doi: 10.1177/21.1.1. [DOI] [PubMed] [Google Scholar]
- Mendes N. F., Musatti C. C., Leão R. C., Mendes E., Naspitz C. K. Lymphocyte cultures and skin allograft survival in patients with South American blastomycosis. J Allergy Clin Immunol. 1971 Jul;48(1):40–45. doi: 10.1016/0091-6749(71)90054-6. [DOI] [PubMed] [Google Scholar]
- Murgita R. A., Tomasi T. B., Jr Suppression of the immune response by alpha-fetoprotein on the primary and secondary antibody response. J Exp Med. 1975 Feb 1;141(2):269–286. doi: 10.1084/jem.141.2.269. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Newberry W. M., Jr, Chandler J. W., Jr, Chin T. D., Kirkpatrick C. H. Immunology of the mycoses. I. Depressed lymphocyte transformation in chronic histoplasmosis. J Immunol. 1968 Feb;100(2):436–443. [PubMed] [Google Scholar]
- Occhino J. C., Glasgow A. H., Cooperband S. R., Mannick J. A., Schmid K. Isolation of an immunosuppressive peptide fraction from human plasma. J Immunol. 1973 Mar;110(3):685–694. [PubMed] [Google Scholar]
- SALVIN S. B., PETERSON R. D., GOOD R. A. THE ROLE OF THE THYMUS IN RESISTANCE TO INFECTION AND ENDOTOXIN TOXICITY. J Lab Clin Med. 1965 Jun;65:1004–1022. [PubMed] [Google Scholar]
- Sjögren H. O., Hellström I., Bansal S. C., Hellström K. E. Suggestive evidence that the "blocking antibodies" of tumor-bearing individuals may be antigen--antibody complexes. Proc Natl Acad Sci U S A. 1971 Jun;68(6):1372–1375. doi: 10.1073/pnas.68.6.1372. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stobo J. D., Rosenthal A. S., Paul W. E. Functional heterogeneity of murine lymphoid cells. V. Lymphocytes lacking detectable surface theta or immunoglobulin determinants. J Exp Med. 1973 Jul 1;138(1):71–88. doi: 10.1084/jem.138.1.71. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Taussig M. J. Demonstration of suppressor T cells in a population of 'educated' T cells. Nature. 1974 Mar 15;248(445):236–238. doi: 10.1038/248236a0. [DOI] [PubMed] [Google Scholar]
- Uhr J. W., Möller G. Regulatory effect of antibody on the immune response. Adv Immunol. 1968;8:81–127. doi: 10.1016/s0065-2776(08)60465-4. [DOI] [PubMed] [Google Scholar]
- Valdimarsson H., Higgs J. M., Wells R. S., Yamamura M., Hobbs J. R., Holt P. J. Immune abnormalities associated with chronic mucocutaneous candidiasis. Cell Immunol. 1973 Mar;6(3):348–361. doi: 10.1016/0008-8749(73)90035-x. [DOI] [PubMed] [Google Scholar]
- Waldmann T. A., Durm M., Broder S., Blackman M., Blaese R. M., Strober W. Role of suppressor T cells in pathogenesis of common variable hypogammaglobulinaemia. Lancet. 1974 Sep 14;2(7881):609–613. doi: 10.1016/s0140-6736(74)91940-0. [DOI] [PubMed] [Google Scholar]
- Wernet P., Kunkel H. G. Antibodies to a specific surface antigen of T cells in human sera inhibiting mixed leukocyte culture reactions. J Exp Med. 1973 Oct 1;138(4):1021–1026. doi: 10.1084/jem.138.4.1021. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Williams R. C., Jr, Lies R. B., Messner R. P. Inhibition of mixed leukocyte culture responses by serum and gamma-globulin fractions from certain patients with connective tissue disorders. Arthritis Rheum. 1973 Sep-Oct;16(5):597–605. doi: 10.1002/art.1780160504. [DOI] [PubMed] [Google Scholar]
- Winfield J. B., Winchester R. J., Wernet P., Fu S. M., Kunkel H. G. Nature of cold-reactive antibodies to lymphocyte surface determinants in systemic lupus erythematosus. Arthritis Rheum. 1975 Jan-Feb;18(1):1–8. doi: 10.1002/art.1780180101. [DOI] [PubMed] [Google Scholar]
- Yachnin S. Fetuin, an inhibitor of lymphocyte transformation. The interaction of fetuin with phytomitogens and a possible role for fetuin in fetal development. J Exp Med. 1975 Jan 1;141(1):242–256. doi: 10.1084/jem.141.1.242. [DOI] [PMC free article] [PubMed] [Google Scholar]