Skip to main content

Advertisement

Log in

Cutaneous Perspectives on Adaptive Immunity

  • Published:
Clinical Reviews in Allergy & Immunology Aims and scope Submit manuscript

Abstract

The skin, situated at the critical juncture between the host and the environment, is subject to a variety of potentially damaging agents including microbial organisms, toxins, and gene-altering radiation. Diverse immunocytes, including those resident in the skin and those with the capacity to traffic to and from the skin, direct two major types of immune responses: more immediate and less discriminate defenses (so-called innate immunity), and more coordinated and antigen-specific responses (so-called adaptive immunity). This review will focus on features of the adaptive immune system operative within the skin and consider the roles of dendritic cells, lymphocytes, endothelial cells, chemokines, and cytokines. In particular, the major subsets of T cells and the mechanisms by which they endow and regulate the features of adaptive immunity in the skin will be considered, including: the efficient surveillance and recognition of diverse foreign-antigens while limiting reactivity against self-antigens; differentiation into various effector cells capable of inducing apoptosis of infected/damaged cells and/or directing the activities of other immunocytes; and providing for immunologic memory whereby subsequent antigen exposure elicits a rapid and augmented antigen-specific response. It is within this context that the adaptive immune system will be considered for its role in the skin in mediating microbial defense with direct relevance to tumor immunosurveillance and inflammatory disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Robert C, Kupper TS (1999) Inflammatory skin diseases, T cells, and immune surveillance. N Engl J Med 341(24):1817–1828

    Article  PubMed  CAS  Google Scholar 

  2. Vishwanath M, Nishibu A, Saeland S et al (2006) Development of intravital intermittent confocal imaging system for studying Langerhans cell turnover. J Invest Dermatol 126:2452–2457

    Article  PubMed  CAS  Google Scholar 

  3. Nishibu A, Ward BR, Jester JV et al (2006) Behavioral responses of epidermal Langerhans cells in situ to local pathological stimuli. J Invest Dermatol 126:787–796

    Article  PubMed  CAS  Google Scholar 

  4. Stingl G, Gazze-Stingl LA, Aberer W, Wolff K (1981) Antigen presentation by murine epidermal Langerhans cells and its alteration by ultraviolet B light. J Immunol 127(4):1707–1713

    PubMed  CAS  Google Scholar 

  5. Bennett CL, van Rijn E, Jung S, Inaba K, Steinman RM, Kapsenberg ML, Clausen BE (2005) Inducible ablation of mouse Langerhans cells diminishes but fails to abrogate contact hypersensitivity. J Cell Biol 169:569–576

    Article  PubMed  CAS  Google Scholar 

  6. Kaplan DH, Jenison MC, Saeland S et al (2005) Immunity 23:611–620

    Article  PubMed  CAS  Google Scholar 

  7. Larrengina AT, Falo LD (2005) Changing paradigms in cutaneous immunology: adapting with dendritic cells. J Invest Dermatol 124(1):1–12

    Article  Google Scholar 

  8. Heath WR, Carbone FR (2003) Dangerous liaisons. Nature 425:460–461

    Article  PubMed  CAS  Google Scholar 

  9. Iwasaki A, Medzhitov R (2004) Toll-like receptor control of the adaptive immune responses. Nat Immunol 5:987–995

    Article  PubMed  CAS  Google Scholar 

  10. Kupper TS (2000) T cells, immunosurveillance, and cutaneous immunity. J Dermatol Sci 24:S41–S45

    Article  PubMed  CAS  Google Scholar 

  11. Clark RA, Chong B, Mirchandani N et al (2006) The vast majority of CLA+ T cells are resident in normal skin. J Immunol 176:4431–4439

    PubMed  CAS  Google Scholar 

  12. Janeway CA, Travers P, Walport M, Shlomchik M (eds) (2005) Immunobiology: the immune system in health and disease, 6th edn. Garland, New York, USA

    Google Scholar 

  13. Girardi M (2006) Immunosurveillance and immunoregulation by γδ T cells. J Invest Dermatol 126:25–31

    Article  PubMed  CAS  Google Scholar 

  14. Shinkai Y, Rathbun G, Lam KP, Oltz EM, Stewart V, Mendelsohn M, Charron J, Datta M, Young F, Stall AM et al (1992) RAG-2-deficient mice lack mature lymphocytes owing to inability to initiate V(D)J rearrangement. Cell 68(5):855–867

    Article  PubMed  CAS  Google Scholar 

  15. Sad S, Marcotte R, Mosmann TR (1995) Cytokine-induced differentiation of precursor mouse CD8+ T cells into cytotoxic CD8+ T cells secreting Th1 or Th2 cytokines. Immunity 2(3):271–279

    Article  PubMed  CAS  Google Scholar 

  16. Renn CN, Sanchez DJ, Ochoa MT, Legaspi AJ, Oh CK, Liu PT, Krutzik SR, Sieling PA, Cheng G, Modlin RL (2006) TLR activation of Langerhans cell-like dendritic cells triggers an antiviral immune response. J Immunol 177(1):298–305

    PubMed  CAS  Google Scholar 

  17. Modlin RL (1994) Th1–Th2 paradigm: insights from leprosy. J Invest Dermatol 102(6):828–832

    Article  PubMed  CAS  Google Scholar 

  18. Saed G, Fivenson DP, Naidu Y, Nickoloff BJ (1994) Mycosis fungoides exhibits a Th1-type cell-mediated cytokine profile whereas Sezary syndrome expresses a Th2-type profile. J Invest Dermatol 103(1):29–33

    Article  PubMed  CAS  Google Scholar 

  19. Biedermann T, Rocken M, Carballido JM (2004) TH1 and TH2 lymphocyte development and regulation of TH cell-mediated immune responses of the skin. J Investig Dermatol Symp Proc 9(1):5–14

    Article  PubMed  CAS  Google Scholar 

  20. Ohmen JD, Hanifin JM, Nickoloff BJ, Rea TH, Wyzykowski R, Kim J, Jullien D, McHugh T, Nassif AS, Chan SC et al (1995) Overexpression of IL-10 in atopic dermatitis. Contrasting cytokine patterns with delayed-type hypersensitivity reactions. J Immunol 154(4):1956–1963

    PubMed  CAS  Google Scholar 

  21. Cookson WO et al (2001) Genetic linkage of childhood atopic dermatitis to psoriasis susceptibility loci. Nat Genet 27:372–373

    Article  PubMed  CAS  Google Scholar 

  22. Palmer CN, Irvine AD, Terron-Kwiatkowski A, Zhao Y, Liao H, Lee SP et al (2006) Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis. Nat Genet 38(4):441–446

    Article  PubMed  CAS  Google Scholar 

  23. Herrick CA, Xu L, McKenzie ANJ et al (2003) IL-13 is necessary, not simply sufficient, for epicutaneously induced Th2 responses to soluble protein antigen. J Immunol 170:2488–2495

    PubMed  CAS  Google Scholar 

  24. Herrick CA, MacLeod H, Glusac E, et al (2000) Th2 responses induced by epicutaneous or inhalational protein exposure are differentially dependent on IL-4. J Clin Invest 105:765–775

    PubMed  CAS  Google Scholar 

  25. Stockinger B, Veldhoen M (2007) Differentiation and function of Th17 T cells. Current Opinion in Immunology 19:281–286

    Google Scholar 

  26. Beissert S, Schwarz A, Schwarz T (2006) Regulatory T cells. J Invest Dermatol 126(1):15–24

    Article  PubMed  CAS  Google Scholar 

  27. Lu L-F, Lind EF, Gondek DC et al (2006) Mast cells are essential intermediaries in regulatory T-cell tolerance. Nature 442:997–1002

    Article  PubMed  CAS  Google Scholar 

  28. La Cava A, Van Kaer L, Shi F-D (2006) CD4+ CD25+ Tregs and NKT cells: regulators regulating regulators. Trends Immunol 27:320–327

    Article  CAS  Google Scholar 

  29. Veldman CM, Gebhard KL, Uter W, Wassmuth R, Grotzinger J, Schultz E, Hertl M (2004) T cell recognition of desmoglein 3 peptides in patients with pemphigus vulgaris and healthy individuals. J Immunol 172(6):3883–3892

    PubMed  CAS  Google Scholar 

  30. Leung DY, Travers JB, Giorno R, Norris DA, Skinner R, Aelion J, Kazemi LV, Kim MH, Trumble AE, Kotb M et al (1995) Evidence for a streptococcal superantigen-driven process in acute guttate psoriasis. J Clin Invest 96(5):2106–2112

    PubMed  CAS  Google Scholar 

  31. Strange P, Skov L, Lisby S, Nielsen PL, Baadsgaard O (1996) Staphylococcal enterotoxin B applied on intact normal and intact atopic skin induces dermatitis. Arch Dermatol 132(1):27–33

    Article  PubMed  CAS  Google Scholar 

  32. Skov L, Baadsgaard O (2000) Bacterial superantigens and inflammatory skin diseases. Clin Exp Dermatol 25(1):57–61

    Article  PubMed  CAS  Google Scholar 

  33. Ackerman AL, Cresswell P (2004) Cellular mechanisms governing cross-presentation of exogenous antigens. Nat Immunol 5:678–684

    Article  PubMed  CAS  Google Scholar 

  34. Hunger RE, Sieling PA, Ochoa MT, Sugaya M, Burdick AE, Rea TH, Brennan PJ, Belisle JT, Blauvelt A, Porcelli SA, Modlin RL (2004) Langerhans cells utilize CD1a and langerin to efficiently present nonpeptide antigens to T cells. J Clin Invest 113(5):701–708

    Article  PubMed  CAS  Google Scholar 

  35. Pennington DJ, Vermijlen D, Wise EL, Clarke SL, Tigelaar RE, Hayday AC (2005) The integration of conventional and unconventional T cells that characterizes cell-mediated responses. Adv Immunol 87:27–59

    Article  PubMed  CAS  Google Scholar 

  36. Girardi M, Oppenheim DE, Steele CR, Lewis JM, Glusac E, Filler R, Hobby P, Sutton B, Tigelaar RE, Hayday AC (2001) Regulation of cutaneous malignancy by γδ T cells. Science 294(5542):605–609

    Article  PubMed  CAS  Google Scholar 

  37. Moris A, Rothenfusser S, Meuer E, Hangretinger R, Fisch P (1999) Role of γδ T cells in tumor immunity and their control by NK receptors. Microbes Infect 1(3):227–234

    Article  PubMed  CAS  Google Scholar 

  38. Holtmeier W, Kabelitz D (2005) γδ T cells link innate and adaptive immune responses. Chem Immunol Allergy 86:151–183

    Article  PubMed  CAS  Google Scholar 

  39. Bonneville M, Fournie JJ (2005) Sensing cell stress and transformation through Vγ9Vδ2 T cell-mediated recognition of the isoprenoid pathway metabolites. Microbes Infect 7(3):503–509

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Michael Girardi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Girardi, M. Cutaneous Perspectives on Adaptive Immunity. Clinic Rev Allerg Immunol 33, 4–14 (2007). https://doi.org/10.1007/s12016-007-0040-9

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12016-007-0040-9

Keywords

Navigation