Human Immunodeficiency Virus Infection and Host Defense in the Lungs

Tysheena P. Charles; Judd E. Shellito

doi:10.1055/s-0036-1572553

Seminars in Respiratory and Critical Care Medicine, Table of Contents

Semin Respir Crit Care Med 2016; 37(02): 147-156
DOI: 10.1055/s-0036-1572553

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Human Immunodeficiency Virus Infection and Host Defense in the Lungs

Authors

Tysheena P. Charles

¹Section of Pulmonary/Critical Care & Allergy/Immunology, Department of Medicine, Louisiana State University Health Sciences Center, New Orleans, Louisiana
Judd E. Shellito

¹Section of Pulmonary/Critical Care & Allergy/Immunology, Department of Medicine, Louisiana State University Health Sciences Center, New Orleans, Louisiana

Abstract

Immunosuppression associated with human immunodeficiency virus (HIV) infection impacts all components of host defense against pulmonary infection. Cells within the lung have altered immune function and are important reservoirs for HIV infection. The host immune response to infected lung cells further compromises responses to a secondary pathogenic insult. In the upper respiratory tract, mucociliary function is impaired and there are decreased levels of salivary immunoglobulin A. Host defenses in the lower respiratory tract are controlled by alveolar macrophages, lymphocytes, and polymorphonuclear leukocytes. As HIV infection progresses, lung CD4 T cells are reduced in number causing a lack of activation signals from CD4 T cells and impaired defense by macrophages. CD8 T cells, on the other hand, are increased in number and cause lymphocytic alveolitis. Specific antibody responses by B-lymphocytes are decreased and opsonization of microorganisms is impaired. These observed defects in host defense of the respiratory tract explain the susceptibility of HIV-infected persons for oropharyngeal candidiasis, bacterial pneumonia, Pneumocystis pneumonia, and other opportunistic infections.

Keywords

HIV infections - host defense against infection - T-lymphocytes - B-lymphocytes - lung infections

Full Text

References

References
1 HIV in the United States | Statistics Overview | Statistics Center | HIV/AIDS | CDC. Estimated HIV incidence among adults and adolescents in the United States, 2007–2010. HIV Surveillance Supplemental Report 2012;17(4). 2015. Available at http://www.cdc.gov/hiv/statistics/basics/ataglance.html
2 Beck JM. Abnormalities in host defense associated with HIV infection. Clin Chest Med 2013; 34 (2) 143-153
3 White NC, Agostini C, Israel-Biet D, Semenzato G, Clarke JR. The growth and the control of human immunodeficiency virus in the lung: implications for highly active antiretroviral therapy. Eur J Clin Invest 1999; 29 (11) 964-972
4 Crowe SM, Carlin JB, Stewart KI, Lucas CR, Hoy JF. Predictive value of CD4 lymphocyte numbers for the development of opportunistic infections and malignancies in HIV-infected persons. J Acquir Immune Defic Syndr 1991; 4 (8) 770-776
5 Shellito JE. Failure of host defenses in human immunodeficiency virus. Semin Respir Crit Care Med 2004; 25 (1) 73-84
6 Kolls JK. CD4(+) T-cell subsets and host defense in the lung. Immunol Rev 2013; 252 (1) 156-163
7 Beck JM. The immunocompromised host: HIV infection. Proc Am Thorac Soc 2005; 2 (5) 423-427
8 Beck JM, Rosen MJ, Peavy HH. Pulmonary complications of HIV infection. Report of the Fourth NHLBI Workshop. Am J Respir Crit Care Med 2001; 164 (11) 2120-2126
9 Rosen MJ. Pulmonary complications of HIV infection. Respirology 2008; 13 (2) 181-190
10 Murray JF. Epidemiology of human immunodeficiency virus-associated pulmonary disease. Clin Chest Med 2013; 34 (2) 165-179
11 Sarkar P, Rasheed HF. Clinical review: respiratory failure in HIV-infected patients—a changing picture. Crit Care 2013; 17 (3) 228
12 Naif HM. Pathogenesis of HIV infection. Infect Dis Rep 2013; 5 (X) (Suppl. 01) e6
13 Milgrim LM, Rubin JS, Small CB. Mucociliary clearance abnormalities in the HIV-infected patient: a precursor to acute sinusitis. Laryngoscope 1995; 105 (11) 1202-1208
14 Montella F, Pezzotti P, Di Sora F, Recchia O, Lauria F, Rezza G. Improving the prognostic value of CD4+ count using IgA and clinical signs in HIV-seropositive i.v. drug users. Infection 1997; 25 (2) 117-120
15 Gordon SB, Read RC. Macrophage defences against respiratory tract infections. Br Med Bull 2002; 61: 45-61
16 Mosser DM. Receptors on phagocytic cells involved in microbial recognition. Immunol Ser 1994; 60: 99-114
17 Iordanskiy S, Santos S, Bukrinsky M. Nature, nurture and HIV: the effect of producer cell on viral physiology. Virology 2013; 443 (2) 208-213
18 Abbas W, Herbein G. T-cell signaling in HIV-1 infection. Open Virol J 2013; 7: 57-71
19 Kumar A, Herbein G. The macrophage: a therapeutic target in HIV-1 infection. Mol Cell Ther 2014; 2: 10
20 Crowe SM, Mills J, Kirihara J, Boothman J, Marshall JA, McGrath MS. Full-length recombinant CD4 and recombinant gp120 inhibit fusion between HIV infected macrophages and uninfected CD4-expressing T-lymphoblastoid cells. AIDS Res Hum Retroviruses 1990; 6 (8) 1031-1037
21 Crowe SM, Mills J, Elbeik T , et al. Human immunodeficiency virus-infected monocyte-derived macrophages express surface gp120 and fuse with CD4 lymphoid cells in vitro: a possible mechanism of T lymphocyte depletion in vivo. Clin Immunol Immunopathol 1992; 65 (2) 143-151
22 Groot F, Welsch S, Sattentau QJ. Efficient HIV-1 transmission from macrophages to T cells across transient virological synapses. Blood 2008; 111 (9) 4660-4663
23 Gendelman HE, Orenstein JM, Martin MA , et al. Efficient isolation and propagation of human immunodeficiency virus on recombinant colony-stimulating factor 1-treated monocytes. J Exp Med 1988; 167 (4) 1428-1441
24 Carter CA, Ehrlich LS. Cell biology of HIV-1 infection of macrophages. Annu Rev Microbiol 2008; 62: 425-443
25 Gavegnano C, Kennedy EM, Kim B, Schinazi RF. The impact of macrophage nucleotide pools on HIV-1 reverse transcription, viral replication, and the development of novel antiviral agents. Mol Biol Int 2012; 2012: 625983
26 Schmidtmayerova H, Alfano M, Nuovo G, Bukrinsky M. Human immunodeficiency virus type 1 T-lymphotropic strains enter macrophages via a CD4- and CXCR4-mediated pathway: replication is restricted at a postentry level. J Virol 1998; 72 (6) 4633-4642
27 Sheehy AM, Gaddis NC, Choi JD, Malim MH. Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein. Nature 2002; 418 (6898) 646-650
28 Neil SJ, Zang T, Bieniasz PD. Tetherin inhibits retrovirus release and is antagonized by HIV-1 Vpu. Nature 2008; 451 (7177) 425-430
29 Hrecka K, Hao C, Gierszewska M , et al. Vpx relieves inhibition of HIV-1 infection of macrophages mediated by the SAMHD1 protein. Nature 2011; 474 (7353) 658-661
30 Lahouassa H, Daddacha W, Hofmann H , et al. SAMHD1 restricts the replication of human immunodeficiency virus type 1 by depleting the intracellular pool of deoxynucleoside triphosphates. Nat Immunol 2012; 13 (3) 223-228
31 Herbein G, Gras G, Khan KA, Abbas W. Macrophage signaling in HIV-1 infection. Retrovirology 2010; 7: 34
32 Das SR, Jameel S. Biology of the HIV Nef protein. Indian J Med Res 2005; 121 (4) 315-332
33 Lamers SL, Fogel GB, Singer EJ , et al. HIV-1 Nef in macrophage-mediated disease pathogenesis. Int Rev Immunol 2012; 31 (6) 432-450
34 Lama J, Mangasarian A, Trono D. Cell-surface expression of CD4 reduces HIV-1 infectivity by blocking Env incorporation in a Nef- and Vpu-inhibitable manner. Curr Biol 1999; 9 (12) 622-631
35 Foster JL, Garcia JV. HIV-1 Nef: at the crossroads. Retrovirology 2008; 5: 84
36 Noonan D, Albini A. From the outside in: extracellular activities of HIV Tat. Adv Pharmacol 2000; 48: 229-250
37 Gautier VW, Gu L, O'Donoghue N, Pennington S, Sheehy N, Hall WW. In vitro nuclear interactome of the HIV-1 Tat protein. Retrovirology 2009; 6: 47
38 Nimmerjahn A, Kirchhoff F, Helmchen F. Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science 2005; 308 (5726) 1314-1318
39 McArthur JC, Hoover DR, Bacellar H , et al. Dementia in AIDS patients: incidence and risk factors. Multicenter AIDS Cohort Study. Neurology 1993; 43 (11) 2245-2252
40 Emerman M. HIV-1, Vpr and the cell cycle. Curr Biol 1996; 6 (9) 1096-1103
41 Dragic T, Litwin V, Allaway GP , et al. HIV-1 entry into CD4+ cells is mediated by the chemokine receptor CC-CKR-5. Nature 1996; 381 (6584) 667-673
42 Subbramanian RA, Kessous-Elbaz A, Lodge R , et al. Human immunodeficiency virus type 1 Vpr is a positive regulator of viral transcription and infectivity in primary human macrophages. J Exp Med 1998; 187 (7) 1103-1111
43 Vodicka MA, Koepp DM, Silver PA, Emerman M. HIV-1 Vpr interacts with the nuclear transport pathway to promote macrophage infection. Genes Dev 1998; 12 (2) 175-185
44 Jacquot G, Le Rouzic E, David A , et al. Localization of HIV-1 Vpr to the nuclear envelope: impact on Vpr functions and virus replication in macrophages. Retrovirology 2007; 4: 84
45 Varin A, Decrion AZ, Sabbah E , et al. Synthetic Vpr protein activates activator protein-1, c-Jun N-terminal kinase, and NF-kappaB and stimulates HIV-1 transcription in promonocytic cells and primary macrophages. J Biol Chem 2005; 280 (52) 42557-42567
46 Faherty CS, Maurelli AT. Staying alive: bacterial inhibition of apoptosis during infection. Trends Microbiol 2008; 16 (4) 173-180
47 Elliott MR, Chekeni FB, Trampont PC , et al. Nucleotides released by apoptotic cells act as a find-me signal to promote phagocytic clearance. Nature 2009; 461 (7261) 282-286
48 Hume DA. Bring out your dead. Nat Immunol 2008; 9 (1) 12-14
49 Kono H, Rock KL. How dying cells alert the immune system to danger. Nat Rev Immunol 2008; 8 (4) 279-289
50 Martin CJ, Booty MG, Rosebrock TR , et al. Efferocytosis is an innate antibacterial mechanism. Cell Host Microbe 2012; 12 (3) 289-300
51 Torre D, Gennero L, Baccino FM, Speranza F, Biondi G, Pugliese A. Impaired macrophage phagocytosis of apoptotic neutrophils in patients with human immunodeficiency virus type 1 infection. Clin Diagn Lab Immunol 2002; 9 (5) 983-986
52 Martin II WJ, Pasula R. Role of alveolar macrophages in host defense against Pneumocystis carinii . Am J Respir Cell Mol Biol 2000; 23 (4) 434-435
53 Mwandumba HC, Squire SB, White SA , et al. Alveolar macrophages from HIV-infected patients with pulmonary tuberculosis retain the capacity to respond to stimulation by lipopolysaccharide. Microbes Infect 2007; 9 (9) 1053-1060
54 Koziel H, Li X, Armstrong MY, Richards FF, Rose RM. Alveolar macrophages from human immunodeficiency virus-infected persons demonstrate impaired oxidative burst response to Pneumocystis carinii in vitro. Am J Respir Cell Mol Biol 2000; 23 (4) 452-459
55 Peebles Jr RS, Graham BS. Viruses, dendritic cells and the lung. Respir Res 2001; 2 (4) 245-249
56 Posch W, Lass-Floörl C, Wilflingseder D. Role of dendritic cell subsets on HIV-specific immunity, current perspectives in HIV infection. In: Saxena SK, ed. 2013. ISBN: 978-953-51-1057-6, InTech. DOI: 10.5772/52744. Available from: http://www.intechopen.com/books/current-perspectives-in-hiv-infection/role-of-dendritic-cell-subsets-on-hiv-specific-immunity
57 Randolph GJ, Ochando J, Partida-Sánchez S. Migration of dendritic cell subsets and their precursors. Annu Rev Immunol 2008; 26: 293-316
58 Siegal FP, Kadowaki N, Shodell M , et al. The nature of the principal type 1 interferon-producing cells in human blood. Science 1999; 284 (5421) 1835-1837
59 Fanning SL, George TC, Feng D , et al. Receptor cross-linking on human plasmacytoid dendritic cells leads to the regulation of IFN-alpha production. J Immunol 2006; 177 (9) 5829-5839
60 Fitzgerald-Bocarsly P, Dai J, Singh S. Plasmacytoid dendritic cells and type I IFN: 50 years of convergent history. Cytokine Growth Factor Rev 2008; 19 (1) 3-19
61 Fazekas de St Groth B. The evolution of self-tolerance: a new cell arises to meet the challenge of self-reactivity. Immunol Today 1998; 19 (10) 448-454
62 Banchereau J, Briere F, Caux C , et al. Immunobiology of dendritic cells. Annu Rev Immunol 2000; 18: 767-811
63 Lambrecht BN, Prins JB, Hoogsteden HC. Lung dendritic cells and host immunity to infection. Eur Respir J 2001; 18 (4) 692-704
64 Manches O, Frleta D, Bhardwaj N. Dendritic cells in progression and pathology of HIV infection. Trends Immunol 2014; 35 (3) 114-122
65 Geijtenbeek TB, Kwon DS, Torensma R , et al. DC-SIGN, a dendritic cell-specific HIV-1-binding protein that enhances trans-infection of T cells. Cell 2000; 100 (5) 587-597
66 Cameron PU, Freudenthal PS, Barker JM, Gezelter S, Inaba K, Steinman RM. Dendritic cells exposed to human immunodeficiency virus type-1 transmit a vigorous cytopathic infection to CD4+ T cells. Science 1992; 257 (5068) 383-387
67 Pope M, Betjes MG, Romani N , et al. Conjugates of dendritic cells and memory T lymphocytes from skin facilitate productive infection with HIV-1. Cell 1994; 78 (3) 389-398
68 Sheehy AM, Gaddis NC, Malim MH. The antiretroviral enzyme APOBEC3G is degraded by the proteasome in response to HIV-1 Vif. Nat Med 2003; 9 (11) 1404-1407
69 Grütter MG, Luban J. TRIM5 structure, HIV-1 capsid recognition, and innate immune signaling. Curr Opin Virol 2012; 2 (2) 142-150
70 Sabado RL, O'Brien M, Subedi A , et al. Evidence of dysregulation of dendritic cells in primary HIV infection. Blood 2010; 116 (19) 3839-3852
71 Donaghy H, Gazzard B, Gotch F, Patterson S. Dysfunction and infection of freshly isolated blood myeloid and plasmacytoid dendritic cells in patients infected with HIV-1. Blood 2003; 101 (11) 4505-4511
72 Kodama A, Tanaka R, Zhang LF , et al. Impairment of in vitro generation of monocyte-derived human dendritic cells by inactivated human immunodeficiency virus-1: Involvement of type I interferon produced from plasmacytoid dendritic cells. Hum Immunol 2010; 71 (6) 541-550
73 Swiecki M, Wang Y, Vermi W, Gilfillan S, Schreiber RD, Colonna M. Type I interferon negatively controls plasmacytoid dendritic cell numbers in vivo. J Exp Med 2011; 208 (12) 2367-2374
74 Ahmed Z, Kawamura T, Shimada S, Piguet V. The role of human dendritic cells in HIV-1 infection. J Invest Dermatol 2015; 135 (5) 1225-1233
75 Banchereau J, Steinman RM. Dendritic cells and the control of immunity. Nature 1998; 392 (6673) 245-252
76 Turville SG, Santos JJ, Frank I , et al. Immunodeficiency virus uptake, turnover, and 2-phase transfer in human dendritic cells. Blood 2004; 103 (6) 2170-2179
77 Wu L, KewalRamani VN. Dendritic-cell interactions with HIV: infection and viral dissemination. Nat Rev Immunol 2006; 6 (11) 859-868
78 Garcia E, Pion M, Pelchen-Matthews A , et al. HIV-1 trafficking to the dendritic cell-T-cell infectious synapse uses a pathway of tetraspanin sorting to the immunological synapse. Traffic 2005; 6 (6) 488-501
79 Choudhuri K, Llodrá J, Roth EW , et al. Polarized release of T-cell-receptor-enriched microvesicles at the immunological synapse. Nature 2014; 507 (7490) 118-123
80 Borregaard N. Neutrophils, from marrow to microbes. Immunity 2010; 33 (5) 657-670
81 Gabelloni ML, Trevani AS, Sabatté J, Geffner J. Mechanisms regulating neutrophil survival and cell death. Semin Immunopathol 2013; 35 (4) 423-437
82 Ellis M, Gupta S, Galant S , et al. Impaired neutrophil function in patients with AIDS or AIDS-related complex: a comprehensive evaluation. J Infect Dis 1988; 158 (6) 1268-1276
83 Lazzarin A, Uberti Foppa C, Galli M , et al. Impairment of polymorphonuclear leucocyte function in patients with acquired immunodeficiency syndrome and with lymphadenopathy syndrome. Clin Exp Immunol 1986; 65 (1) 105-111
84 Murphy PM, Lane HC, Fauci AS, Gallin JI. Impairment of neutrophil bactericidal capacity in patients with AIDS. J Infect Dis 1988; 158 (3) 627-630
85 Nielsen H, Kharazmi A, Faber V. Blood monocyte and neutrophil functions in the acquired immune deficiency syndrome. Scand J Immunol 1986; 24 (3) 291-296
86 Pitrak DL, Bak PM, DeMarais P, Novak RM, Andersen BR. Depressed neutrophil superoxide production in human immunodeficiency virus infection. J Infect Dis 1993; 167 (6) 1406-1410
87 Pitrak DL, Tsai HC, Mullane KM, Sutton SH, Stevens P. Accelerated neutrophil apoptosis in the acquired immunodeficiency syndrome. J Clin Invest 1996; 98 (12) 2714-2719
88 Fichtenbaum CJ, Woeltje KF, Powderly WG. Serious Pseudomonas aeruginosa infections in patients infected with human immunodeficiency virus: a case-control study. Clin Infect Dis 1994; 19 (3) 417-422
89 Day CL, Kaufmann DE, Kiepiela P , et al. PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression. Nature 2006; 443 (7109) 350-354
90 Brenchley JM, Karandikar NJ, Betts MR , et al. Expression of CD57 defines replicative senescence and antigen-induced apoptotic death of CD8+ T cells. Blood 2003; 101 (7) 2711-2720
91 El-Far M, Halwani R, Said E , et al. T-cell exhaustion in HIV infection. Curr HIV/AIDS Rep 2008; 5 (1) 13-19
92 Rosignoli G, Cranage A, Burton C , et al. Expression of PD-L1, a marker of disease status, is not reduced by HAART in aviraemic patients. AIDS 2007; 21 (10) 1379-1381
93 Freeman GJ, Long AJ, Iwai Y , et al. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med 2000; 192 (7) 1027-1034
94 Carter L, Fouser LA, Jussif J , et al. PD-1:PD-L inhibitory pathway affects both CD4(+) and CD8(+) T cells and is overcome by IL-2. Eur J Immunol 2002; 32 (3) 634-643
95 Keir ME, Butte MJ, Freeman GJ, Sharpe AH. PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol 2008; 26: 677-704
96 Wherry EJ, Ha SJ, Kaech SM , et al. Molecular signature of CD8+ T cell exhaustion during chronic viral infection. Immunity 2007; 27 (4) 670-684
97 Bowers NL, Helton ES, Huijbregts RP, Goepfert PA, Heath SL, Hel Z. Immune suppression by neutrophils in HIV-1 infection: role of PD-L1/PD-1 pathway. PLoS Pathog 2014; 10 (3) e1003993
98 Mortha A, Diefenbach A. Natural killer cell receptor-expressing innate lymphocytes: more than just NK cells. Cell Mol Life Sci 2011; 68 (21) 3541-3555
99 Shi F-D, Ljunggren H-G, La Cava A, Van Kaer L. Organ-specific features of natural killer cells. Nat Rev Immunol 2011; 11 (10) 658-671
100 Stegmann KA, Björkström NK, Veber H , et al. Interferon-alpha-induced TRAIL on natural killer cells is associated with control of hepatitis C virus infection. Gastroenterology 2010; 138 (5) 1885-1897
101 Kelly MN, Zheng M, Ruan S, Kolls J, D'Souza A, Shellito JE. Memory CD4+ T cells are required for optimal NK cell effector functions against the opportunistic fungal pathogen Pneumocystis murina . J Immunol 2013; 190 (1) 285-295
102 Moll M, Snyder-Cappione J, Spotts G, Hecht FM, Sandberg JK, Nixon DF. Expansion of CD1d-restricted NKT cells in patients with primary HIV-1 infection treated with interleukin-2. Blood 2006; 107 (8) 3081-3083
103 Sandberg JK, Fast NM, Palacios EH , et al. Selective loss of innate CD4(+) V α 24 natural killer T cells in human immunodeficiency virus infection. J Virol 2002; 76 (15) 7528-7534
104 Motsinger A, Haas DW, Stanic AK, Van Kaer L, Joyce S, Unutmaz D. CD1d-restricted human natural killer T cells are highly susceptible to human immunodeficiency virus 1 infection. J Exp Med 2002; 195 (7) 869-879
105 van der Vliet HJ, von Blomberg BM, Hazenberg MD , et al. Selective decrease in circulating V alpha 24+V beta 11+ NKT cells during HIV type 1 infection. J Immunol 2002; 168 (3) 1490-1495
106 Giorgi JV, Hultin LE, McKeating JA , et al. Shorter survival in advanced human immunodeficiency virus type 1 infection is more closely associated with T lymphocyte activation than with plasma virus burden or virus chemokine coreceptor usage. J Infect Dis 1999; 179 (4) 859-870
107 Sousa AE, Carneiro J, Meier-Schellersheim M, Grossman Z, Victorino RM. CD4 T cell depletion is linked directly to immune activation in the pathogenesis of HIV-1 and HIV-2 but only indirectly to the viral load. J Immunol 2002; 169 (6) 3400-3406
108 Taylor JM, Fahey JL, Detels R, Giorgi JV. CD4 percentage, CD4 number, and CD4:CD8 ratio in HIV infection: which to choose and how to use. J Acquir Immune Defic Syndr 1989; 2 (2) 114-124
109 Zaman MM, Recco RA, Raguthu L, Likki S, Reddy S. Characteristics of HIV-1-infected patients with CD4:CD8 lymphocyte ratio normalization on antiretroviral therapy. AIDS Patient Care STDS 2000; 14 (12) 647-649
110 Margolick JB, Gange SJ, Detels R, O'Gorman MR, Rinaldo Jr CR, Lai S. Impact of inversion of the CD4/CD8 ratio on the natural history of HIV-1 infection. J Acquir Immune Defic Syndr 2006; 42 (5) 620-626
111 Pahwa S, Read JS, Yin W , et al; Women and Infants Transmission Study. CD4+/CD8+ T cell ratio for diagnosis of HIV-1 infection in infants: Women and Infants Transmission Study. Pediatrics 2008; 122 (2) 331-339
112 Amadori A, Zamarchi R, De Silvestro G , et al. Genetic control of the CD4/CD8 T-cell ratio in humans. Nat Med 1995; 1 (12) 1279-1283
113 Tang J, Li X, Price MA , et al. CD4:CD8 lymphocyte ratio as a quantitative measure of immunologic health in HIV-1 infection: findings from an African cohort with prospective data. Front Microbiol 2015; 6: 670
114 Neff CP, Chain JL, MaWhinney S , et al. Lymphocytic alveolitis is associated with the accumulation of functionally impaired HIV-specific T cells in the lung of antiretroviral therapy-naive subjects. Am J Respir Crit Care Med 2015; 191 (4) 464-473
115 Twigg HL, Soliman DM, Day RB , et al. Lymphocytic alveolitis, bronchoalveolar lavage viral load, and outcome in human immunodeficiency virus infection. Am J Respir Crit Care Med 1999; 159 (5, Pt 1) 1439-1444
116 Ho DD, Neumann AU, Perelson AS, Chen W, Leonard JM, Markowitz M. Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection. Nature 1995; 373 (6510) 123-126
117 Nakayama-Hosoya K, Ishida T, Youngblood B , et al. Epigenetic repression of interleukin 2 expression in senescent CD4+ T cells during chronic HIV type 1 infection. J Infect Dis 2015; 211 (1) 28-39
118 Nakayama K, Nakamura H, Koga M , et al. Imbalanced production of cytokines by T cells associates with the activation/exhaustion status of memory T cells in chronic HIV type 1 infection. AIDS Res Hum Retroviruses 2012; 28 (7) 702-714
119 Giuliani E, Vassena L, Cerboni C, Doria M. Release of soluble ligands for the activating NKG2D receptor: one more immune evasion strategy evolved by HIV-1?. Curr Drug Targets 2015; 17 (1) 54-64
120 Fry TJ, Mackall CL. The many faces of IL-7: from lymphopoiesis to peripheral T cell maintenance. J Immunol 2005; 174 (11) 6571-6576
121 Schluns KS, Kieper WC, Jameson SC, Lefrançois L. Interleukin-7 mediates the homeostasis of naïve and memory CD8 T cells in vivo. Nat Immunol 2000; 1 (5) 426-432
122 Tan JT, Dudl E, LeRoy E , et al. IL-7 is critical for homeostatic proliferation and survival of naive T cells. Proc Natl Acad Sci U S A 2001; 98 (15) 8732-8737
123 Tan JT, Ernst B, Kieper WC, LeRoy E, Sprent J, Surh CD. Interleukin (IL)-15 and IL-7 jointly regulate homeostatic proliferation of memory phenotype CD8+ cells but are not required for memory phenotype CD4+ cells. J Exp Med 2002; 195 (12) 1523-1532
124 Lang KS, Recher M, Navarini AA , et al. Inverse correlation between IL-7 receptor expression and CD8 T cell exhaustion during persistent antigen stimulation. Eur J Immunol 2005; 35 (3) 738-745
125 Koesters SA, Alimonti JB, Wachihi C , et al. IL-7Ralpha expression on CD4+ T lymphocytes decreases with HIV disease progression and inversely correlates with immune activation. Eur J Immunol 2006; 36 (2) 336-344
126 Boutboul F, Puthier D, Appay V , et al. Modulation of interleukin-7 receptor expression characterizes differentiation of CD8 T cells specific for HIV, EBV and CMV. AIDS 2005; 19 (17) 1981-1986
127 Golden-Mason L, Burton Jr JR, Castelblanco N , et al. Loss of IL-7 receptor alpha-chain (CD127) expression in acute HCV infection associated with viral persistence. Hepatology 2006; 44 (5) 1098-1109
128 Crawley AM, Angel JB. The influence of HIV on CD127 expression and its potential implications for IL-7 therapy. Semin Immunol 2012; 24 (3) 231-240
129 Moir S, Fauci AS. B cells in HIV infection and disease. Nat Rev Immunol 2009; 9 (4) 235-245
130 Wilkes DS, Weissler JC. Alloantigen-induced immunoglobulin production in human lung: differential effects of accessory cell populations on IgG synthesis. Am J Respir Cell Mol Biol 1994; 10 (3) 339-346
131 Twigg III HL, Spain BA, Soliman DM, Bowen LK, Heidler KM, Wilkes DS. Impaired IgG production in the lungs of HIV-infected individuals. Cell Immunol 1996; 170 (1) 127-133
132 Lane HC, Masur H, Edgar LC, Whalen G, Rook AH, Fauci AS. Abnormalities of B-cell activation and immunoregulation in patients with the acquired immunodeficiency syndrome. N Engl J Med 1983; 309 (8) 453-458
133 Baughman RP, Thorpe JE, Staneck J, Rashkin M, Frame PT. Use of the protected specimen brush in patients with endotracheal or tracheostomy tubes. Chest 1987; 91 (2) 233-236
134 Thorpe JE, Baughman RP, Frame PT, Wesseler TA, Staneck JL. Bronchoalveolar lavage for diagnosing acute bacterial pneumonia. J Infect Dis 1987; 155 (5) 855-861
135 Lozupone C, Cota-Gomez A, Palmer BE , et al; Lung HIV Microbiome Project. Widespread colonization of the lung by Tropheryma whipplei in HIV infection. Am J Respir Crit Care Med 2013; 187 (10) 1110-1117