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Vol. 3. Issue 5.
Pages 461-471 (September - October 1997)
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Vol. 3. Issue 5.
Pages 461-471 (September - October 1997)
ARTIGO ORIGINAL
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Sobre a presença de Células T CD45RA + na Pleurisia Tuberculosa*
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A. Segorbe Luis
Centro de Pneumologia da Universidade de Coimbra.
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RESUMO

A circulação de linfócitos tem como fins biológicos assegurar a oferta de especificidadcs dos seus receptores antigénicos e unificar funcionalmente os diversos compartimentos linfóides. Aumenta-se, assim, a probabilidade de um reduzido número de células " naïve" poder encontrar o epitopo antigénico especifico e promove-se a oferta de receptores antigénicos de células "memoria" e efectoras nos tecidos, de forma a assegurar a vigilância imune.

Tem prevalecido a ideia de que os linfócitos T " naïve", virgens da activação antigénica, tendem a migrar sistematicamente para o tecido linfóide secundário (gânglios linfáticos, placas de Peyer, amígdalas, …), onde transitam para o estadio de "memória" num ambiente diferenciado para a apresentação antigénica.

Na fase maturativa de " memória", os linfócitos T adquirem a capacidade de domiciliação para o compartimento linfóide terciário (pele, mucosas,…). A migração de linfócitos "memoria" para os tecidos vem a desempenbar um papel fundamental na defesa a agressores microbianos, designadamente na génese das respostas secundárias.

A pleurisia tuberculosa constitui-se em resultado da reacção de hipersensibilidade a antigénios micobacterianos. Nesta forma de pleurite é suposto que ocorram localmente respostas por linfócitos já condicionados antigenicamente e que seja favorecida a migração local de linfócitos efectores e "memória".

Através da marcação com o anticorpo monoclonal 2H4, específico do antigénio de diferenciação CD45RA, com elevada expressão em células "naïve", o presente estudo permitiu demonstrar que 28% dos linfócitos T de exsudados pleurais de etiologia tuberculosa evidenciavam esta característica fenotípica.

Corrobora-se a hipótese da existência de um afluxo de linfócitos "naïve" para os tecidos em que decorre um processo imunoinflamatório.

Tal ocorrência, ao ter sido verifieada na pleurisia tuberculosa, vem questionar a noção de que o tráfego linfocitário seja exclusivo de linfócitos efectores e "memória" quando estão em causa respostas celulares de perfil Th1 na serosa pleural.

O facto das células CD45RA encerrarem em si a possibilidade de diferenciação em células efectoras Th 1 ou Th2, é provável que o ambiente citocínico existente na pleurisia tuberculosa condicione a sua maturação para celulas Th1. No entanto, sendo conhecida a vocação "Th2" das células CD45RA+, será também de considerar a sua possível intervenção na produção local de citocinas inibidoras da actividade de clãs Th1.

SUMMARY

CD45RA+T CELLS ARE PRESENT IN TUBERCULOUS PLEU­RAL EXUDATES

Lymphocyte circulation and diapedesis have as biological aims the insurance of the availability of antigen receptors as well as the functional unification of the various lymphoid compartments. Thus, the probability of a small number of "naive" cells being able to a encounter their specific antigen epitope is increased and the supply of antigen receptors on "memory" and effector cells to peripheral tissues is optimized.

It is generally accepted that "naïve" T lymphocytes, virgin in terms of antigenic stimulation, tend to sistematically migrate into secondary lymphoyd tissues (lymph nodes, Peyer patches, tonsils, …), where they become "memory" cells in a milieu differenciated towards antigen presentation. As "memory" cells, T lymphocytes acquire the capacity to migrate into tertiary lymphoyd compartments (skin, mucosae, …). The migration of "memory" lymphocytes into tissues plays a crucial role in the defense against microbes, namely in the generation of secondary responses.

Tuberculous pleurisy occurs as result of a hypersensitivity reaction to mycobacterial antigens. In this form of pleuritis, local responses mediated by lymphocytes that have already been antigen primed are believed to occur and to be favoured by the local migration of effector and "memory" lymphocytes.

In our phenotypic study using monoclonal antibody 2H4, specific for the differentiation antigen CD45RA, which is highly expressed on "naive" cells, has demonstrated that 28% of T lymphocytes present in pleural tuberculous exudates were positive for this marker.

These results support the hypothesis that an influx of "naïve" lymphocytes may occur into tissues with an ongoing inflammatory process. This observation questions the notion that lymphocyte migration is restricted to effector and "memory" lymphocytes in Th1-type cellular responses, as occurs in tuberculous pleurisy.

As CD45RA+ cells have the intrinsic capacity to develop onto Th 1 or T h2 effector cells, they are probably oriented in pleura to acquire a type 1 cytokine profile. Otherwise, CD45RA+ cells could be committed to act in situ as Th2 effector cells, secreting Th1-inibhitory cytokines.

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BIBLIOGRAFIA
[1.]
J.L. Gowans.
The lymphocyte - a disgraceful gap in medical knowledge.
Immunol Today, 17 (1996), pp. 288
[2.]
T.A. Springer.
Adhesion Receptors of the Immune System.
Nature, 346 (1990), pp. 425
[3.]
J.P. Girard, T.A. Springer.
High endothelial venules (HEVs): specialized endothelium for lymphocyte migration.
Immunol Today, 16 (1995), pp. 449
[4.]
C.R. MacKay.
Homing of natïve, memory and effector lymphocytes.
Curr Opinion Immunol., 5 (1993), pp. 423
[5.]
C.R. MacKay, B.A. Imhof.
Cell adhesion in the immune system.
Immunol Today, 14 (1993), pp. 99
[6.]
N. Hogg.
Roll, roll, roll your leukocyte gently down the veim.
Immunol Today, 13 (1992), pp. 113
[7.]
M.P. Bevilacqua.
Endothehai-Leukocyte Adhesion Molecules.
Ann Rev Immunol, 11 (1993), pp. 767
[8.]
D.H. Adams, S. Shaw.
Leucocyte -endothelial interactions and regulation of leukocyte migration.
Lancet, 343 (1994), pp. 831
[9.]
R. Pardi, L. Inverardy, J.R. Bender.
Regulatory mechanisms in leukocyte adhesion: flexible receptors for sophisticated travelers.
Immunol Today, 13 (1992), pp. 224
[10.]
Y. Shimilu, W. Newman, Y. Tanaka, S. Shaw.
Lymphocyte interactions with endothelials cells.
Immunol Today, 13 (1992), pp. 106
[11.]
L.M. Bradley, M. Croft, S.L. Swain.
T-cell memory: new perspectives.
Immunol Today, 14 (1993), pp. 197
[12.]
L.J. Picker.
Control of lymphocyte homing.
Curr Opinion Immunol, 6 (1994), pp. 394
[13.]
J. Westermann, R. Pabst.
How organ-specific is the migration of "naïve" and "memory" T cells.
Immunol Today, 17 (1996), pp. 279
[14.]
A. Górsky.
The role of cell adhesion molecules in immunopathology.
Immunol Today, 15 (1994), pp. 251
[15.]
C. Saltini, M. Kirby, Trapnell, N. Tamura, R.G. Crystal.
Biased accumulation of T lymphocytes with "memory"-type CD45 leukocyte common gene expression on the epithelial surface of the human lung.
J Exp Med, 171 (1990), pp. 1123
[16.]
T. Pettersson.
Cellular Immunity.
pp. 329
[17.]
A. Segorbe Luis.
Quelques aspects de l'immunité au cours des épanchements pleuraux.
Mémoire pour le Titre d'Assistant Étranger, Académic de Paris, Université René­Descartes, (1986),
[18.]
Luis A. Segorue.
Reactividade dos Linfócitos T na Pleurisin Tuberculosa Humana".
Dissertacção de Doutora-mento, Faculdade de Medicina, Universidade de Coimbra, (1991),
[19.]
H. Fujiwara, Y. Okuda, T. Fukukawa, I. Tsuyuguchi.
In vitro tuberculin reactivity of lymphocytes from patients with tuberculous pleurisy.
Infect and Immun;, 35 (1980), pp. 402
[20.]
T. Pettersson, M. Klockars, H. Riska.
PHA and PPD reactivity of lymphocytcs in pleural effusions.
Chest, 80 (1981), pp. 44
[21.]
I. Ocaña, J. Martinez-Vasquez, R. Segura, T. Fernandez-de-Sevilha, J. Capdevila.
Adenosine deaminase in pleural fluids. Test for diagnosis of tuberculous pleural effusion.
Chest, 84 (1983), pp. 51
[22.]
Hernando H., Jimenez J., Dominguez-Juncal L., Garcia-Buela P., Egaña M. Bueso J. Meaning and diagnostic value of determining the lisozyme level of pleural fluid.
[23.]
H. Riska, T. Pettersson, B. Froseth, M. Klockars.
Beta 2 microglobulin in pleural effusions.
Acta Med Scand, 21 (1982), pp. 45
[24.]
E. Ribera, T. Español, J. M-Vasquez, I. Ocaña, G. Encabo.
Lymphocyte Proliferation and gamma­ Interferon production after "in vitro" stimulation with PPD. Differences between tuberculous and nontuberculous pleurisy in patients with positive tuberculin skin test.
Chest, 97 (1990), pp. 1381
[25.]
E. Ribera, I. Ocaña, J. Martinez-Vasquez, M. Rossell, Español, A. Ruibal.
High level of Interferon-y in tuberculous pleural effusion.
Chest, 2 (1988), pp. 309
[26.]
I. Tachibana, T. Kokubu.
Elevated levels of soluble Interleukin-2 receptors in tuberculous pleural effusions.
Chest, 97 (1990), pp. 1141
[27.]
P. Barnes, R. Modlin, D. Bikle, J. Adams.
Transpleural gradient of 1,25-dydroxyvitamin D in tuberculous pleuritis.
J Clin Invest, 83 (1989), pp. 1527
[28.]
F. Barnes, S. Mistry, C. Cooper, C. Pirmez, T. Rea, R. Modlin.
Compartmentalization of a CD4 lymphocyte subpopulation in tuberculous pleuritis.
J Immunol;, 142 (1989), pp. 1114
[29.]
P.F. Barnes, S.J. Fong, P.J. Brennan, P.E. Twomey, A. Mazunder, R.L. Modlin.
Local production of Tumor Necrosis Factor and Interferon-γ in Tuberculous Pleuritis.
J. Immunol, 145 (1990), pp. 149
[30.]
G. Del Prete, M. De Carli, C. Mastromauro, R. Biagiotti, D. Macchia, P. Falaglani, M. Ricci, S. Romagnagni.
Purified Protein Derivative of Myco-bacterium tuberculosis and excretory-secretory antigen(s) of Toxocara canis expand in vitro human T cells with stable and opposite (Type 1T helper or Type 2T helper) profile of cytokine production.
J. Clin. Invest., 88 (1991), pp. 346
[31.]
M. Zhang, M.K. Gately, E. Wang, J. Gong, S.F. Wolf, S. Lu, R.F. Modlin, P.F. Barnes.
Interleukin 12 at site of disease in tuberculosis.
J Clin Invest, 93 (1994), pp. 1733
[32.]
T.R. Mosman, S. Sad.
The expanding universe of T-cell subsets: Th1, Th2 and more.
Immunol Today, 17 (1996), pp. 138
[33.]
E.N.T. Meeusen, R.R. Premier, M.R. Brandon.
Tissue-specific migration of lymphocytes: a key role for Th1 and Th2 cells?.
Immunol Today., 17 (1996), pp. 421
[34.]
E. Ruoslahti.
Integrins.
J Clin Invest, 87 (1991), pp. 1
[35.]
N. Hogg, J. Harvey, C. Cabanas, R.C. Landis.
Control of leukocyte integrin activation.
Am Rev Respir Dis, 148 (1993), pp. S55
[36.]
J.M. Pilewsky, S.M. Albelda.
Adhesion molecules in the lung: an overview.
Am Rev Respir Dis, 148 (1993), pp. S31
[37.]
L. Lasky.
Selectins: Interpreters of cell-specifc Carbohydrate Information During Inflammation.
Science, 258 (1992), pp. 964
[38.]
M.P. Bevilacqua, R.M. Nelson.
Selectins.
J Clin Invest, 91 (1993), pp. 379
[39.]
R.P. McEver.
Selectins.
Curr Opinion Immunol, 6 (1994), pp. 75
[40.]
H.M. Delisser, P.J. Newman, S.M. Albelda.
Moiecular and functional aspects of PECAM-1/CD31.
Immunol Today, 15 (1994), pp. 490
[41.]
L.M. Bradley, S.R. Watson.
Lymphocyte migration into tissue: the paradigm derived from CD4 subsets.
Curr Opinion Immunol, 8 (1996), pp. 312
[42.]
U. Schauer, T. Jung, C.H.L. Rieger.
Imbalance of CD4+CD45R+ and CD4+CD29+ T helper subsets in patients with atopic diseases.
Clin Exp Immunol, 83 (1991), pp. 25
[43.]
A. Daser, N. Meissner, U. Herz, H. Renz.
Role and modulation of T-cell cytokines in allergy.
Curr Opinion in Immunol, 7 (1995), pp. 762
[44.]
P.F. Barnes, S. Lu, J.S. Abrams, E. Wang, M. Yamamu­Ra, R.L. Modlin.
Cytokine production at the site of disease in human tuberculosis.
Infect Immun, 61 (1993), pp. 3482-3489

Reflexão, à luz dos conhecimentos actuais, sobre alguns dados do trabalho, "Estudo da Reactividade dos Linfócitos T na Pleurisia Tuberculosa Humana", Dissertação de Doutoramento do autor. Universidade de Coimbra, 1991.

Copyright © 1997. Sociedade Portuguesa de Pneumologia/SPP
Pulmonology
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