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. 1992 Apr;75(4):576–581.

Antigen-presentation by macrophages but not by dendritic cells in human immunodeficiency virus (HIV) infection.

S E Macatonia 1, M Gompels 1, A J Pinching 1, S Patterson 1, S C Knight 1
PMCID: PMC1384833  PMID: 1534309

Abstract

Dendritic cells (DC) have a potent antigen-presenting capacity for recruiting resting T cells into immune responses. They also promote expansion of already activated memory T cells. By contrast, macrophages (M phi) are only effective in stimulating memory responses. Infection and depletion of DC occur in human immunodeficiency virus (HIV)-infected individuals and recruitment of T cells into primary responses is blocked. Here comparisons between DC and M phi in stimulating secondary T-cell responses in HIV infection were made. Adherent M phi, and DC isolated by a new method, were separated from peripheral blood of patients in different stages of HIV infection and from uninfected controls and added to allogeneic lymphocytes in mixed leucocyte reactions (MLR). Some were pulsed with influenza virus or tetanus toxoid and used to stimulate autologous T cells. Responses were measured from uptake of [3H]thymidine in 20 microliters hanging drop cultures. DC, but not M phi, from normal individuals stimulated MLR but both populations stimulated secondary responses to recall antigens. DC from all HIV seropositive individuals caused little or no stimulation of any lymphocyte responses. However, M phi from HIV seropositive asymptomatic individuals and those with persistent generalized lymphadenopathy stimulated responses to recall antigens. There was no stimulation using cells from acquired immune deficiency syndrome (AIDS) patients. Blocked DC but not M phi function may underlie progressive immunological non-responsiveness in HIV infection. Without recruitment of resting T cells, loss of memory T cells may be cumulative; failure of secondary activation (e.g. by M phi) would lead to lost T-cell activity. Identification and circumvention of the defect in DC could offer new therapeutic approaches.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Armstrong J. A., Horne R. Follicular dendritic cells and virus-like particles in AIDS-related lymphadenopathy. Lancet. 1984 Aug 18;2(8399):370–372. doi: 10.1016/s0140-6736(84)90540-3. [DOI] [PubMed] [Google Scholar]
  2. Belsito D. V., Sanchez M. R., Baer R. L., Valentine F., Thorbecke G. J. Reduced Langerhans' cell Ia antigen and ATPase activity in patients with the acquired immunodeficiency syndrome. N Engl J Med. 1984 May 17;310(20):1279–1282. doi: 10.1056/NEJM198405173102002. [DOI] [PubMed] [Google Scholar]
  3. Braathen L. R., Ramirez G., Kunze R. O., Gelderblom H. Langerhans cells as primary target cells for HIV infection. Lancet. 1987 Nov 7;2(8567):1094–1094. doi: 10.1016/s0140-6736(87)91526-1. [DOI] [PubMed] [Google Scholar]
  4. Dréno B., Milpied B., Bignon J. D., Stalder J. F., Litoux P. Prognostic value of Langerhans cells in the epidermis of HIV patients. Br J Dermatol. 1988 Apr;118(4):481–486. doi: 10.1111/j.1365-2133.1988.tb02456.x. [DOI] [PubMed] [Google Scholar]
  5. Eales L. J., Farrant J., Helbert M., Pinching A. J. Peripheral blood dendritic cells in persons with AIDS and AIDS related complex: loss of high intensity class II antigen expression and function. Clin Exp Immunol. 1988 Mar;71(3):423–427. [PMC free article] [PubMed] [Google Scholar]
  6. Hughes R. A., Macatonia S. E., Rowe I. F., Keat A. C., Knight S. C. The detection of human immunodeficiency virus DNA in dendritic cells from the joints of patients with aseptic arthritis. Br J Rheumatol. 1990 Jun;29(3):166–170. doi: 10.1093/rheumatology/29.3.166. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. Janossy G., Pinching A. J., Bofill M., Weber J., McLaughlin J. E., Ornstein M., Ivory K., Harris J. R., Favrot M., Macdonald-Burns D. C. An immunohistological approach to persistent lymphadenopathy and its relevance to AIDS. Clin Exp Immunol. 1985 Feb;59(2):257–266. [PMC free article] [PubMed] [Google Scholar]
  9. Kanitakis J., Thivolet J. Infection of human epidermal Langerhans' cells by HIV. AIDS. 1990 Mar;4(3):266–268. [PubMed] [Google Scholar]
  10. Kanitakis J., Thivolet J. Infection of human epidermal Langerhans' cells by HIV. AIDS. 1990 Mar;4(3):266–268. [PubMed] [Google Scholar]
  11. Knight S. C., Macatonia S. E., Patterson S. HIV I infection of dendritic cells. Int Rev Immunol. 1990;6(2-3):163–175. doi: 10.3109/08830189009056627. [DOI] [PubMed] [Google Scholar]
  12. Lane H. C., Depper J. M., Greene W. C., Whalen G., Waldmann T. A., Fauci A. S. Qualitative analysis of immune function in patients with the acquired immunodeficiency syndrome. Evidence for a selective defect in soluble antigen recognition. N Engl J Med. 1985 Jul 11;313(2):79–84. doi: 10.1056/NEJM198507113130204. [DOI] [PubMed] [Google Scholar]
  13. Leonard J., Khillan J. S., Gendelman H. E., Adachi A., Lorenzo S., Westphal H., Martin M. A., Meltzer M. S. The human immunodeficiency virus long terminal repeat is preferentially expressed in Langerhans cells in transgenic mice. AIDS Res Hum Retroviruses. 1989 Aug;5(4):421–430. doi: 10.1089/aid.1989.5.421. [DOI] [PubMed] [Google Scholar]
  14. Macatonia S. E., Lau R., Patterson S., Pinching A. J., Knight S. C. Dendritic cell infection, depletion and dysfunction in HIV-infected individuals. Immunology. 1990 Sep;71(1):38–45. [PMC free article] [PubMed] [Google Scholar]
  15. Macatonia S. E., Patterson S., Knight S. C. Suppression of immune responses by dendritic cells infected with HIV. Immunology. 1989 Jul;67(3):285–289. [PMC free article] [PubMed] [Google Scholar]
  16. Macatonia S. E., Taylor P. M., Knight S. C., Askonas B. A. Primary stimulation by dendritic cells induces antiviral proliferative and cytotoxic T cell responses in vitro. J Exp Med. 1989 Apr 1;169(4):1255–1264. doi: 10.1084/jem.169.4.1255. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Meltzer M. S., Skillman D. R., Gomatos P. J., Kalter D. C., Gendelman H. E. Role of mononuclear phagocytes in the pathogenesis of human immunodeficiency virus infection. Annu Rev Immunol. 1990;8:169–194. doi: 10.1146/annurev.iy.08.040190.001125. [DOI] [PubMed] [Google Scholar]
  18. Oxholm P., Helweg-Larsen S., Permin H. Immunohistological skin investigations in patients with the acquired immune deficiency syndrome. Acta Pathol Microbiol Immunol Scand A. 1986 Mar;94(2):113–116. doi: 10.1111/j.1699-0463.1986.tb02972.x. [DOI] [PubMed] [Google Scholar]
  19. Patterson S., Gross J., Bedford P., Knight S. C. Morphology and phenotype of dendritic cells from peripheral blood and their productive and non-productive infection with human immunodeficiency virus type 1. Immunology. 1991 Mar;72(3):361–367. [PMC free article] [PubMed] [Google Scholar]
  20. Patterson S., Knight S. C. Susceptibility of human peripheral blood dendritic cells to infection by human immunodeficiency virus. J Gen Virol. 1987 Apr;68(Pt 4):1177–1181. doi: 10.1099/0022-1317-68-4-1177. [DOI] [PubMed] [Google Scholar]
  21. Pinching A. J., Nye K. E. Defective signal transduction--a common pathway for cellular dysfunction in HIV infection? Immunol Today. 1990 Jul;11(7):256–259. doi: 10.1016/0167-5699(90)90100-n. [DOI] [PubMed] [Google Scholar]
  22. Ranki A., Valle S. L., Krohn M., Antonen J., Allain J. P., Leuther M., Franchini G., Krohn K. Long latency precedes overt seroconversion in sexually transmitted human-immunodeficiency-virus infection. Lancet. 1987 Sep 12;2(8559):589–593. doi: 10.1016/s0140-6736(87)92985-0. [DOI] [PubMed] [Google Scholar]
  23. Rappersberger K., Gartner S., Schenk P., Stingl G., Groh V., Tschachler E., Mann D. L., Wolff K., Konrad K., Popovic M. Langerhans' cells are an actual site of HIV-1 replication. Intervirology. 1988;29(4):185–194. doi: 10.1159/000150045. [DOI] [PubMed] [Google Scholar]
  24. Rosenberg Z. F., Fauci A. S. The immunopathogenesis of HIV infection. Adv Immunol. 1989;47:377–431. doi: 10.1016/s0065-2776(08)60665-3. [DOI] [PubMed] [Google Scholar]
  25. Shearer G. M., Bernstein D. C., Tung K. S., Via C. S., Redfield R., Salahuddin S. Z., Gallo R. C. A model for the selective loss of major histocompatibility complex self-restricted T cell immune responses during the development of acquired immune deficiency syndrome (AIDS). J Immunol. 1986 Oct 15;137(8):2514–2521. [PubMed] [Google Scholar]
  26. Silberberg-Sinakin I., Gigli I., Baer R. L., Thorbecke G. J. Langerhans cells: role in contact hypersensitivity and relationship to lymphoid dendritic cells and to macrophages. Immunol Rev. 1980;53:203–232. doi: 10.1111/j.1600-065x.1980.tb01045.x. [DOI] [PubMed] [Google Scholar]
  27. Tschachler E., Groh V., Popovic M., Mann D. L., Konrad K., Safai B., Eron L., diMarzo Veronese F., Wolff K., Stingl G. Epidermal Langerhans cells--a target for HTLV-III/LAV infection. J Invest Dermatol. 1987 Feb;88(2):233–237. doi: 10.1111/1523-1747.ep12525402. [DOI] [PubMed] [Google Scholar]
  28. van Noesel C. J., Gruters R. A., Terpstra F. G., Schellekens P. T., van Lier R. A., Miedema F. Functional and phenotypic evidence for a selective loss of memory T cells in asymptomatic human immunodeficiency virus-infected men. J Clin Invest. 1990 Jul;86(1):293–299. doi: 10.1172/JCI114698. [DOI] [PMC free article] [PubMed] [Google Scholar]

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