Skip to main content
SpringerLink
Log in

Lymphocytes in the lung: an often neglected cell

Numbers, characterization and compartmentalization

  • Review Article
  • Published:
Anatomy and Embryology Aims and scope Submit manuscript

Abstract

The lung is continuously in contact with inhaled particles, some of which are of microbial origin. This requires adequate defence mechanisms in the form of immune reactions. These can be subdivided into the afferent and efferent limb. Specific immune reactions depend on the interactions between lymphoid and accessory cells. Therefore, the local histotopographic localization of lymphocyte subsets has to be known to understand pulmonary immune reactions. As lymphocytes have often not been mentioned when cells in the respiratory tract have been characterized, their compartmentalization, number and subset composition in the lung are outlined here. Lymphocytes are found in the epithelium and lamina propria of the bronchi with different subset compositions. In some species, like the rabbit, bronchus-associated lymphoid tissue (BALT) is found as follicle-like aggregations with lymphocytes infiltrating the epithelium, which shows specialized epithelial cells. BALT, however, is not a constitutive structure in all species, e.g in humans. Nevertheless, certain (probably) microbial stimuli can induce BALT in adult humans. In contrast to many other organs, the lung vascular bed contains large numbers of lymphocytes. Little is known about the adhesion molecules that make this margination possible. In the lung interstitium about 10×109 lymphocytes have been calculated for healthy adults. The most easily accessible pool of lymphocytes in the human lung are those recovered by bronchoalveolar lavage. The vast majority of such lymphocytes express markers typical for “memory lymphocytes”. The intrapulmonary migratory routes of lymphocytes and the integration of the lung in the common mucosal immune system are described. A multicompartmental model for lymphocytes is outlined as a basis for understanding lung diseases such as asthma.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Adams DH, Shaw S (1994) Leucocyte-endothelial interactions and regulation of leucocyte migration. Lancet 343:831–836

    Google Scholar 

  • Berman JS, Beer DJ, Theodore AC, Kornfeld H, Bernardo J, Center DM (1990) Lymphocyte recruitment to the lung. Am Rev Respir Dis 142:238–257

    Google Scholar 

  • Bice DE, Muggenburg BA (1988) Localized immune memory in the lung. Am Rev Respir Dis 138:565–571

    Google Scholar 

  • Bice DE, Jones SE, Muggenburg BA (1993) Long-term antibody production after lung immunization and challenge: role of lung and lymphoid tissues. Am J Respir Cell Mol Biol 8:662–667

    Google Scholar 

  • Bienenstock J (1984) Immunology of the lung and upper respiratory tract. McGraw Hill, New York

    Google Scholar 

  • Binns RM, Licence ST, Pabst R (1992) Homing of blood, splenic and lung emigrant lymphoblasts: comparison with the behaviour of lymphocytes from these sources. Int Immunol 4:1011–1019

    Google Scholar 

  • Burns AR, Takei F, Doerschuk CM (1994) Quantitation of ICAM1 expression in mouse lung during pneumonia. J Immunol 153:3189–3198

    Google Scholar 

  • Corrigan CJ, Kay AB (1992) T cells and eosinophils in the pathogenesis of asthma. Immunol Today 13:501–507

    Google Scholar 

  • Curtis JL, Kim S, Scott PJ, Buechner-Maxwell VA (1995) Adhesion receptor phenotypes of murine lung CD4+ T cells during the pulmonary immune response to sheep erythrocytes. Am J Respir Cell Mol Biol 12:520–530

    Google Scholar 

  • Dunkley M, Pabst R, Cripps A (1995) An important role for intestinally derived T cells in respiratory defence. Immunol Today 16:231–236

    Google Scholar 

  • Erle DJ, Brown T, Christian D, Aris R (1994) Lung epithelial lining fluid T cell subsets defined by distinct patterns of β7 and β1 integrin expression. Am J Respir Cell Mol Biol 10:237–244

    Google Scholar 

  • Ermert L, Seeger W, Duncker HR (1993) Computer-assisted morphometry of the intracapillary leukocyte pool in the rabbit lung. Cell Tissue Res 271:469–476

    Google Scholar 

  • Ermert L, Duncker HR, Rosseau S, Schütte H, Seeger W (1994) Morphometric analysis of pulmonary intracapillary leukocyte pools in ex vivo-perfused rabbit lungs. Am J Physiol 267:L64-L70

    Google Scholar 

  • Fajac I, Tazi A, Hance AJ, Bouchonnet F, Riquet M, Battesti JP, Soler P (1992) Lymphocytes infiltrating normal human lung and lung carcinomas rarely express gamma delta T cell antigen receptors. Clin Exp Immunol 87:127–131

    Google Scholar 

  • Fliegert F, Tschernig T, Pabst R (1995) Comparison of lymphocyte subsets from three lung compartments with the peripheral blood in the rat. Am J Respir Crit Care Med 151:A35

    Google Scholar 

  • Fournier M, Lebargy F, Le Roy Ladurie F, Lenormand E, Pariente R (1989) Intraepithelial T-lymphocyte subsets in the airways of normal subjects and of patients with chronic bronchitis. Am Rev Respir Dis 140:737–742

    Google Scholar 

  • Gail DB, Lenfant CJM (1983) Cells of the lung: biology and clinical implications. Am Rev Respir Dis 127:366–387

    Google Scholar 

  • Gebert A, Rothkötter HJ, Pabst R (1995) M cells in Peyer's patches of the intestine. Int Rev Cytol (in press)

  • Gosset P, Tillie-Leblond I, Janin A, Marquette CH, Copin MC, Wallaert B, Tonnel AB (1995) Expression of E-selectin, ICAM-1 and VCAM-1 on bronchial biopsies from allergic and non-allergic asthmatic patients. Int Arch Allergy Immunol 106:69–77

    Google Scholar 

  • Haley PJ (1993) Immunological responses within the lung after inhalation of airborne chemicals. In: Gardner DE et al (eds) Toxicology of the lung, 2nd edn. Raven Press, New York, pp 389–416

    Google Scholar 

  • Hamacher J, Schaberg T (1994) Adhesion molecules in lung diseases. Lung 172:189–213

    Google Scholar 

  • Hamann A, Andrew DP, Jablonski-Westrich D, Holzmann B, Butcher EC (1994) Role of alpha4-integrins in lymphocyte homing to mucosal tissues in vivo. J Immunol 152:3282–3293

    Google Scholar 

  • Hance AJ (1993) Pulmonary immune cells in health and disease: dendritic cells and Langerhans' cells. Eur Respir J 6:1213–1220

    Google Scholar 

  • Hogg JC (1991) Neutrophil traffic. In: Crystal RG, West JB (eds) The lung: scientific foundations. Raven Press, New York, pp 565–579

    Google Scholar 

  • Holt PG, Robinson BWS, Reid M, Kees UR, Warton A, Dawson VH, Rose A, Schon-Hegrad M, Papadimitriou JM (1986) Extraction of immune and inflammatory cells from human lung parenchyma: evaluation of an enzymatic digestion procedure. Clin Exp Immunol 66:188–200

    Google Scholar 

  • Holt PG, Schon-Hegrad MA, McMenamin PG (1990) Dendritic cells in the respiratory tract. Int Rev Immunol 6:139–149

    Google Scholar 

  • Holt PG, Haining S, Nelson DJ, Sedgwick JD (1994) Origin and steady-state turnover of class II MHC-bearing dendritic cells in the epithelium of the conducting airways. J Immunol 153:256–261

    Google Scholar 

  • Hunninghake GW, Kawanami O, Ferrans VJ, Young RC, Roberts WC, Crystal RG (1981) Characterization of the inflammatory and immune effector cells in the lung parenchyma of patients with interstitial lung disease. Am Rev Respir Dis 123:407–412

    Google Scholar 

  • Kolopp-Sarda MN, Bene MC, Massin N, Moulin JJ, Faure GC (1994) Immunohistological analysis of macrophages, B-cells, and T-cells in the mouse lung. Anat Rec 239:150–157

    Google Scholar 

  • Kraehenbuhl JP, Neutra MR (1992) Molecular and cellular basis of immune protection of mucosal surfaces. Physiol Rev 72:853–879

    Google Scholar 

  • Kroemer G, de Alboran IM, Gonzalo JA, Martinez-A C (1993) Immunoregulation by cytokines. Crit Rev Immunol 13:163–191

    Google Scholar 

  • Mason MJ, Gillett NA, Bice DE (1989) Comparison of systemic and local immune responses after multiple pulmonary antigen exposures. Reg Immunol 2:149–157

    Google Scholar 

  • McDermott MR, Bienenstock J (1979) Evidence for a common mucosal immunologic system. I. Migration of B immunoblasts into intestinal, respiratory, and genital tissues. J Immunol 122:1892–1898

    Google Scholar 

  • McWilliam AS, Nelson D, Thomas JA, Holt PG (1994) Rapid dendritic cell recruitment is a hallmark of the acute inflammatory response at mucosal surfaces. J Exp Med 179:1331–1336

    Google Scholar 

  • Morin MJ, Warner A, Fields BN (1994) A pathway for entry of reoviruses into the host through M cells of the respiratory tract. J Exp Med 180:1523–1527

    Google Scholar 

  • Mulligan MS, Vaporciyan AA, Warner RL, Jones ML, Foreman KE, Miyasaka M, Todd RF, Ward PA (1995) Compartmentalized roles for leukocytic adhesion molecules in lung inflammatory injury. J Immunol 154:1350–1363

    Google Scholar 

  • Pabst R (1990) Compartmentalization and kinetics of lymphoid cells in the lung. Reg Immunol 3:62–71

    Google Scholar 

  • Pabst R (1992) Is BALT a major component of the human lung immune system? Immunol Today 13:119–122

    Google Scholar 

  • Pabst R (1995a) Mucosa-associated lymphoid tissue. Only one part of the dynamic lung lymphoid system. In: Holgate ST, Busse WW (eds) Asthma and rhinitis. Blackwell, Cambridge, MA, pp 415–425

    Google Scholar 

  • Pabst R (1995b) Localization and dynamics of lymphoid cells in the different compartments of the lung. In: Burnett D, Stockley RA (eds) Pulmonary defences. Wiley, Chichester (in press)

    Google Scholar 

  • Pabst R, Binns RM (1995) Lymphocytes migrate from the bronchoalveolar space to regional bronchial lymph nodes. Am J Respir Crit Care Med 151:495–499

    Google Scholar 

  • Pabst R, Gehrke I (1990) Is the bronchus-associated lymphoid tissue (BALT) an integral structure of the lung in normal mammals including man? Am J Respir Cell Mol Biol 3:131–135

    Google Scholar 

  • Pabst R, Binns RM, Licence ST, Peter M (1987) Evidence of a selective major vascular marginal pool of lymphocytes in the lung. Am Rev Respir Dis 136:1213–1218

    Google Scholar 

  • Picker JL (1994) Control of lymphocyte homing. Curr Opin Immunol 6:394–406

    Google Scholar 

  • Pilewski JM, Albelda SM (1995) Cell adhesion molecules in asthma: homing, activation, and airway remodeling. Am J Respir Cell Mol Biol 12:1–3

    Google Scholar 

  • Pretolani M, Ruffié C, Lapa ne Silva JR, Joseph D, Lobb RR, Vargaftig BB (1994) Antibody to very late activation antigen 4 prevents antigen-induced bronchial hyperreactivity and cellular infiltration in the guinea pig airways. J Exp Med 180:795–805

    Google Scholar 

  • Reynolds HY (1994) Respiratory host defenses — surface immunity. Immunobiology 191:402–412

    Google Scholar 

  • Richmond I, Pritchard GE, Ashcroft T, Avery A, Corris PA, Walters EH (1993) Bronchus-associated lymphoid tissue (BALT) in human lung: its distribution in smokers and non-smokers. Thorax 48:1130–1134

    Google Scholar 

  • Saltini C, Hemler ME, Crystal RG (1988) T lymphocytes compartmentalized on the epithelial surface of the lower respiratory tract express the very late activation antigen complex VLA1. Clin Immunol Immunopathol 46:221–233

    Google Scholar 

  • Saltini C, Kirby M, Trapnell BC, Tamura N, Crystal RG (1990) Biased accumulation of T lymphocytes with “memory”-type CD45 leukocyte common antigen gene expression on the epithelial surface of the human lung. J Exp Med 171:1123–1140

    Google Scholar 

  • Saltini C, Richeldi L, Holroyd KJ, DuBois RM, Crystal RG (1991) Lymphocytes. In: Crystal RG, West JB (eds) The lung: scientific foundations. Raven Press, New York, pp 459–482

    Google Scholar 

  • Semenzato G (1991) Immunology of interstitial lung diseases: cellular events taking place in the lung of sarcoidosis, hypersensitivity pneumonitis and HIV infection. Eur Respir J 4:94–102

    Google Scholar 

  • Semenzato G, Chilosi M, Ossi E, Trentin L, Pizzolo G, Cipriani A, Agostini C, Zambello R, Marcer G, Gasparotto G (1985) Bronchoalveolar lavage and lung histology. Comparative analysis of inflammatory and immunocompetent cells in patients with sarcoidosis and hypersensitivity pneumonitis. Am Rev Respir Dis 132:400–404

    Google Scholar 

  • Sminia T, Brugge-Gamelkoorn GJ, Jeurissen SHM (1989) Structure and function of bronchus-associated lymphoid tissue (BALT). Crit Rev Immunol 9:119–150

    Google Scholar 

  • Soutar CA (1976) Distribution of plasma cells and other cells containing immunoglobulin in the respiratory tract of normal man and class of immunoglobulin therein. Thorax 31:158–166

    Google Scholar 

  • Springer TA (1994) Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm. Cell 76:301–314

    Google Scholar 

  • Tschernig T, Kleemann WJ, Pabst R (1995) Bronchus-associated lymphoid tissue (BALT) in the lungs of children who had died from sudden infant death syndrome and other causes. Thorax 50:658–660

    Google Scholar 

  • Upham JW, McMenamin C, Schon-Hegrad MA, Robinson BWS, Holt PG (1994) Functional analysis of human bronchial mucosal T cells extracted with interleukin-2. Am J Respir Crit Care Med 149:1608–1613

    Google Scholar 

  • Walker C, Bode E, Boer L, Hansel TT, Blaser K, Virchow JC (1992) Allergic and nonallergic asthmatics have distinct patterns of T-cell activation and cytokine production in peripheral blood and bronchoalveolar lavage. Am Rev Respir Dis 146:109–115

    Google Scholar 

  • Wegner CD, Gundel RH, Rothlein R, Letts LG (1992) Expression and probable roles of cell adhesion molecules in lung inflammation. Chest 101:34S-39S

    Google Scholar 

  • Weissler JC, Nicod LP, Lipscomb MF, Toews GB (1987) Natural killer cell function in human lung is compartmentalized. Am Rev Respir Dis 135:941–949

    Google Scholar 

  • Weissman DN, Bice DE, Muggenburg BA, Haley PJ, Shopp GM, Schuyler MR (1992) Primary immunization in the canine lung. Soluble antigen induces a localized response. Am Rev Respir Dis 145:6–12

    Google Scholar 

  • Weissman DN, Bice DE, Crowell RE, Schuyler MR (1994) Intrapulmonary antigen deposition in the human lung: local responses. Am J Respir Cell Mol Biol 11:607–614

    Google Scholar 

  • Weisz-Carrington P, Roux ME, McWilliams M, Phillips-Quagliata JM, Lamm ME (1979) Organ and isotype distribution of plasma cells producing specific antibody after oral immunization: evidence for a generalized secretory immune system. J Immunol 123:1705–1708

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Centre of Anatomy 4120, Medical School of Hannover, D-30623, Hannover, Germany

    R. Pabst & T. Tschernig

Authors
  1. R. Pabst
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. T. Tschernig
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pabst, R., Tschernig, T. Lymphocytes in the lung: an often neglected cell. Anat Embryol 192, 293–299 (1995). https://doi.org/10.1007/BF00710098

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00710098

Key words

Search

Navigation