Evaluación de las subpoblaciones de linfocitos T en pacientes tuberculosos empleand la modulación con teofilina

Dlugovitzky, Diana; Huber, K.; Welker, G.; Molteni, O.

doi:10.1590/S0036-46651991000200004

Resúmenes

Se evaluaron las poblaciones y subpoblaciones linfocitarias en pacientes con tuberculosis pulmonar antes y durante la terapia relacionando estos valores con la incidencia y evolución de la enfermedad. Pacientes en sus diversas manifestaciones clínicas, vírgenes de tratamiento, se estudiaron por baciloscopía (BAAR), radiología, i.d.r. Mantoux y análisis complementarios. Se cuantificaron mediante la prueba de Rosetas espontáneas (RE) linfocitos T totales y activos (RE a 4ºC y 37ºC), T colaboradores (RE Teofilina Resistentes: RETR) y supresores (RE Teofilina Sensibles: RETS). Los exámenes se repitieron en los mismos sujetos iniciado el tratamiento y en testigos sanos (TS). Se demostró en los pacientes en todas sus formas clínicas un descenso significativo en los valores relativos y absolutos de células T y en la relación RETR/RETS (menor de 1). Existe asociación entre la forma clínica y el número de linfocitos T colaboradores. Los pacientes en tratamiento con evolución favorable, evidenciaron un incremento significativo en los linfocitos T totales, activos, colaboradores y en la relación RETR/RETS. Los enfermos con baciloscopía altamente positiva presentaron i.d.r. Mantoux baja o negativa y marcado descenso de células inmunocompetentes. Se comprobó asociación entre estas tres variables, lo mismo que entre el estado nutricional y la predisposición a contraer la enfermedad.

Tuberculosis; Subpoblaciones de linfocitos T; Teofilina

T cells and T cells subsets in peripheral blood of patients with different forms of pulmonary tuberculosis were evaluated to explain some aspects of the immunocompromised state of these subjects. Diagnosis was made by baciloscopy (BAAR), chest roentgenography i.d.r Mantoux, and other clinical analysis. Spontaneous E-Rosette test (RE) was used to quantify Total (RET 4ºC) and Active T cells (REA 37ºC) and the same test after incubation with Theophilline (The) for helper cells (The-re-sistant cells: RETR) and suppressor cells (The-sensitive cells: RETS). Patients were followed for at least 4 months after therapy. The data demonstrate a significant decrease of relative and absolute numbers of Total T-cells and a diminished T helper/T suppressor subset ratio (RETR/RETS) which dropped to less than 1 in untreated patients. Treated patients with a favourable evolution showed a restoration of Total active and helper T cells. RETR/RETS ratio was also significantly increased. In patients with highly positive BAAR, low on negative i.d.r Mantoux, a decreased level of immunocompetent cells was observed. The 3 aspects were associated. Nutritional condition of the patients wal also associated with the predisposition to acquire this disease.

IMUNOLOGIA

Evaluación de las subpoblaciones de linfocitos T en pacientes tuberculosos empleand la modulación con teofilina

T lymphocyte subsets evaluation in patients with pulmonary tuberculosis using theophylline modulation

Diana Dlugovitzky^I; K. Huber^II; G. Welker^III; O. Molteni^IV

^IInvestigadora del Consejo de Investigaciones de la U.N.R. Docente de la Cátedra de Microbiologia, a cargo de la Sección Inmunología. Facultad de Ciencias Médicas. Universidad Nacional de Rosario. Rosario, Argentina

^IIDocente e Investigadora de la Cátedra de Microbiología. Facultad de Ciencias Médicas. Universidad Nacional de Rosario. Rosario, Argentina

^IIIMédico del Hospital de Enfermedades Infecciosas V. L. Carrasco. Docente Cátedra de Enfermedades Infecciosas. Facultad de Ciencias Médicas. Universidad Nacional de Rosario. Rosario, Argentina

^IVProfessor Titular de la Cátedra de Microbiología, Parasitología y Virología. Facultad de Ciencias Médicas. Universidad Nacional de Rosario. Rosario, Argentina

^{Dirección para la Correspondencia} Dirección para la Correspondencia: Dra. Diana Dlugovitzky Maipú 1340 P. Baja Dto. "D" 2000 Rosario - Argentina

RESUMEN

Se evaluaron las poblaciones y subpoblaciones linfocitarias en pacientes con tuberculosis pulmonar antes y durante la terapia relacionando estos valores con la incidencia y evolución de la enfermedad.

Pacientes en sus diversas manifestaciones clínicas, vírgenes de tratamiento, se estudiaron por baciloscopía (BAAR), radiología, i.d.r. Mantoux y análisis complementarios.

Se cuantificaron mediante la prueba de Rosetas espontáneas (RE) linfocitos T totales y activos (RE a 4ºC y 37ºC), T colaboradores (RE Teofilina Resistentes: RETR) y supresores (RE Teofilina Sensibles: RETS). Los exámenes se repitieron en los mismos sujetos iniciado el tratamiento y en testigos sanos (TS).

Se demostró en los pacientes en todas sus formas clínicas un descenso significativo en los valores relativos y absolutos de células T y en la relación RETR/RETS (menor de 1). Existe asociación entre la forma clínica y el número de linfocitos T colaboradores.

Los pacientes en tratamiento con evolución favorable, evidenciaron un incremento significativo en los linfocitos T totales, activos, colaboradores y en la relación RETR/RETS.

Los enfermos con baciloscopía altamente positiva presentaron i.d.r. Mantoux baja o negativa y marcado descenso de células inmunocompetentes. Se comprobó asociación entre estas tres variables, lo mismo que entre el estado nutricional y la predisposición a contraer la enfermedad.

Unitermos: Tuberculosis; Subpoblaciones de linfocitos T; Teofilina.

SUMMARY

T cells and T cells subsets in peripheral blood of patients with different forms of pulmonary tuberculosis were evaluated to explain some aspects of the immunocompromised state of these subjects.

Diagnosis was made by baciloscopy (BAAR), chest roentgenography i.d.r Mantoux, and other clinical analysis.

Spontaneous E-Rosette test (RE) was used to quantify Total (RET 4ºC) and Active T cells (REA 37ºC) and the same test after incubation with Theophilline (The) for helper cells (The-re-sistant cells: RETR) and suppressor cells (The-sensitive cells: RETS). Patients were followed for at least 4 months after therapy.

The data demonstrate a significant decrease of relative and absolute numbers of Total T-cells and a diminished T helper/T suppressor subset ratio (RETR/RETS) which dropped to less than 1 in untreated patients.

Treated patients with a favourable evolution showed a restoration of Total active and helper T cells. RETR/RETS ratio was also significantly increased.

In patients with highly positive BAAR, low on negative i.d.r Mantoux, a decreased level of immunocompetent cells was observed. The 3 aspects were associated.

Nutritional condition of the patients wal also associated with the predisposition to acquire this disease.

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Recebido para publicação em 21/6/1990.

Aceito para publicação em 1/3/1991.

1. ALLEN, E.M.; STERNICK, J.L.; SCHRIER, D.J. & MOORE, V.L. BCG induced chronic pulmonary inflamation and splenomegaly in mice: suppression of PHA induced proliferation delayed hypersensitivity to sheep erytrocy-tes and chronic pulmonar inflammation by soluble factors from adherent spleen cells. Cell. Immunol., 58: 61-71, 1981.
2. BOOM, W.H.; HUSSON, R.N.; YOUNG, R.A.; DAVID, J.R. & PIESSENS, W.F. In vivo and in vitro characterization of murine T cell clones reactive to Mycobacterium tuberculosis. Infect. Immun., 83: 7013-7117,1987.
3. COLLINS, F.M. & CAMPBELL, S.G. Immunity to intracellular bacteria. Vet. Immunol. Immunopath., 3: 5-66, 1982.
4. COOMBS, R.R.A.; GURNER, B.W.; WILSON, A.B.; HOLM, G. & LUSCHGRIN, B. Rosette information between human lymphocytes and sheep red cells not involving immunoglobulin receptors. Int. Arch. Allergy, 39: 658-665, 1970.
5. DANIEL, T.M. The immunology of tuberculosis. Clin. Chest Med., 1: 189-201, 1980.
6. DANIEL, T.M.; OXTOBY, M.J.; PINTO, R. & MORENO, E. The immune spectrum in patients with pulmonary tuberculosis. Amer. Rev. resp. Dis., 123: 556-559, 1981.
7. DANNEMBERG, A.M. Pathogenesis of tuberculosis: native and acquired resistence in animals and humans microbiology. Washington, American Society for Microbiology, 1984. p. 344-354.
8. DANNEMBERG, JR, A.M. Pathogenesis of pulmonary tuberculosis. In: FISHMAN, A.P., ed. Pulmonary diseases and disorders. 2 nd. ed. New York, Mac Graw-Hill, 1988. p. 1821-1842.
9. DE LIBERO, G.; FLESCH, I. & KAUFMANN, S.H.E. Mycobacteria reactive Lyt 2⁺ T-cell lines. Europ. J. Immunol., 18: 59-66, 1987.
10. ELLNER, J.J. & WALLIS, R.S. Immunologic aspects of mycobacterial infections. Rev. infect. Dis., 11 (Suppl. 2): S455-S459, 1989.
11. ESTRADA PARRA, S. La respuesta inmunológica en la tuberculosis. Salud publ. Méx., 25: 403-409, 1983.
12. FUJIWARA, H.; OKUDA, T.; FUKUKAWA, T. & TSUYOGUCH, I. In vitro tuberculin reactivity of lymphocyte from patients with tuberculosis pleuresy. Infect. Immun., 35: 402-409, 1982.
13. HAHN, H. & KAUFMANN, S.H.E. The role of cell-mediated immunity in bacterial infections. Rev. infect. Dis., 3: 1221-1250, 1981.
14. KAUFMANN, S.H.E. & FLESCH, I. Function and antigen recognition pattern of L₃T₄ T-cells clones from Mycobacterium tuberculosis immune mice. Infect. Immun., 54: 291-296, 1986.
15. KAUFMANN, S.H.E.; VATH, V.; THOLE, J.E.R.; VAN EMBDEN, J.D.A. & EMMRICH, F. Enumeration of T cells reactive with Mycobacterium tuberculosis organisms and specific for the recombinant mycobacterial 64-KDa protein. Europ. J. Immunol., 17: 351-357, 1987.
16. KAUFMANN, S.H.E. - In vitro analysis of the cellular mechanisms involved in immunity to tuberculosis. Rev. infect. Dis., 11 (Suppl. 2): S448-S459, 1989.
17. KLEINHENZ, M.E. & ELLNER, J.J. Antigen responsiveness during tuberculosis: regulatory interactions of T cell subpopulations and adherent cells. J. Lab. clin. Med., 110: 31-40, 1987.
18. LAMB, J.R.; IVANYI, J.; REES, A.; YOUNG, R.A. & YOUNG, A.B. - The identification of T cells, epitopes in Mycobacterium tuberculosis using human T lymphocyte clones. Leprosy Rev., 57: 131-137, 1986.
19. LIMAMBUL, S.; SHORE, A.; DOSCH, N.M. & GELFAND, W. Theophylline modulation of E rosette formations: an indicator of T-cell maturation. Clin. exp. Immunol., 33: 503-508, 1978.
20. MÜLLER, I.; COBBOLD, S.P.; WALDMAN, H. & KAUFMANN, S.H.E. Impaired resistance to Mycobacterium tuberculosis infection after selective in-vivo depletion of L₃T₄ and Lyt2⁺ T cells. Infect. Immun., 55: 2037-2041, 1987.
21. OFTUNG, F.; MUSTAFA, A.S.; HUSSON, R.A. & GODAL, T. Human T cell clones recognize two abundant Mycobacterium tuberculosis protein antigens expressed in Escherichia coli. J. Immunol., 138: 927-931, 1987.
22. ORME, I.A. & COLLINS, F.M. Adoptive protection of Mycobacterium tuberculosis infected lung: dissociation between cells that passively transfer protective immunity and those that transfer delayed-type hipersensitivity to tuberculin. Cell. Immunol., 84: 113-120, 1984.
23. ORME, I.M. The kinetics of emergence and loss of mediator T lymphocytes acquired in response to infection with Mycobacterium tuberculosis. J. Immunol., 138: 293-298, 1987.
24. PIESSENS, W.F. Introduction to the immunology of tuberculosis. Rev. infect. Dis., 11 (Suppl. 2): S436-S441, 1989.
25. ROOK, G.A.W. Role of activated macrophages in the immunology of tuberculosis. Brit. med. Bull., 44: 611-623, 1988.
26. ROOK, G.A.W.; CARSWELL, J.W. & STANFORD, J.J. Preliminary evidence for trapping of antigen specific lymphocytes in the lymphoid tissue of anergic tuberculosis patients. Clin. exp. Immunol., 26: 129-132, 1976.
27. SHOAT, B. & JOSHNA, H. Supressor helper and immu-noregulatory T cells in normal human blood as defined by theophylline sensitivity. Thymus, 4: 323, 1982.
28. SMITH, D.W. & WEIEGESHAUS, E.H. - What animal models can teach us about the pathogenesis of tuberculosis in man. Rev. infect. Dis., 11 (Suppl. 2): S385-S393, 1989.
29. STEEL, J.; FLINT, K.C.; POZNICK, A.L.; HUDSPITH, B.; JOHNSON, M.M. & ROOK, G.A.W. Inhibition of virulent Mycobacteria tuberculosis by murine peritoneal macrophages and human alveolar lavage cells. The effect of lymphokines and recombinant gamma interferon. Tubercle, 67: 289-294, 1986.
30. VRIES, R.R.P. Regulation of T cell responsiveness against mycobacterial antigens by HLA class 2 immune response genes. Rev. infect. Dis., 11 (Suppl. 2): S400-S403, 1989.
31. WYBRAM, J. The human rosette forming cells as a marker of a population of thymus derived cells. J. clin. Invest., 51: 2537-2545, 1972.
32. WYBRAM, J. Rosette forming cells in immunologic defficience diseases and transferfactor. New Engl. J. Med., 281: 710-716, 1973.

Dirección para la Correspondencia:

Dra. Diana Dlugovitzky

Maipú 1340

P. Baja Dto. "D"

2000 Rosario - Argentina

Fechas de Publicación

Publicación en esta colección
12 Set 2006
Fecha del número
Abr 1991

Histórico

Recibido
21 Jun 1991
Acepto
01 Mar 1991

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

[1] 1. ALLEN, E.M.; STERNICK, J.L.; SCHRIER, D.J. & MOORE, V.L. BCG induced chronic pulmonary inflamation and splenomegaly in mice: suppression of PHA induced proliferation delayed hypersensitivity to sheep erytrocy-tes and chronic pulmonar inflammation by soluble factors from adherent spleen cells. Cell. Immunol., 58: 61-71, 1981.

[2] 2. BOOM, W.H.; HUSSON, R.N.; YOUNG, R.A.; DAVID, J.R. & PIESSENS, W.F. In vivo and in vitro characterization of murine T cell clones reactive to Mycobacterium tuberculosis. Infect. Immun., 83: 7013-7117,1987.

[3] 3. COLLINS, F.M. & CAMPBELL, S.G. Immunity to intracellular bacteria. Vet. Immunol. Immunopath., 3: 5-66, 1982.

[4] 4. COOMBS, R.R.A.; GURNER, B.W.; WILSON, A.B.; HOLM, G. & LUSCHGRIN, B. Rosette information between human lymphocytes and sheep red cells not involving immunoglobulin receptors. Int. Arch. Allergy, 39: 658-665, 1970.

[5] 5. DANIEL, T.M. The immunology of tuberculosis. Clin. Chest Med., 1: 189-201, 1980.

[6] 6. DANIEL, T.M.; OXTOBY, M.J.; PINTO, R. & MORENO, E. The immune spectrum in patients with pulmonary tuberculosis. Amer. Rev. resp. Dis., 123: 556-559, 1981.

[7] 7. DANNEMBERG, A.M. Pathogenesis of tuberculosis: native and acquired resistence in animals and humans microbiology. Washington, American Society for Microbiology, 1984. p. 344-354.

[8] 8. DANNEMBERG, JR, A.M. Pathogenesis of pulmonary tuberculosis. In: FISHMAN, A.P., ed. Pulmonary diseases and disorders. 2 nd. ed. New York, Mac Graw-Hill, 1988. p. 1821-1842.

[9] 9. DE LIBERO, G.; FLESCH, I. & KAUFMANN, S.H.E. Mycobacteria reactive Lyt 2⁺ T-cell lines. Europ. J. Immunol., 18: 59-66, 1987.

[10] 10. ELLNER, J.J. & WALLIS, R.S. Immunologic aspects of mycobacterial infections. Rev. infect. Dis., 11 (Suppl. 2): S455-S459, 1989.

[11] 11. ESTRADA PARRA, S. La respuesta inmunológica en la tuberculosis. Salud publ. Méx., 25: 403-409, 1983.

[12] 12. FUJIWARA, H.; OKUDA, T.; FUKUKAWA, T. & TSUYOGUCH, I. In vitro tuberculin reactivity of lymphocyte from patients with tuberculosis pleuresy. Infect. Immun., 35: 402-409, 1982.

[13] 13. HAHN, H. & KAUFMANN, S.H.E. The role of cell-mediated immunity in bacterial infections. Rev. infect. Dis., 3: 1221-1250, 1981.

[14] 14. KAUFMANN, S.H.E. & FLESCH, I. Function and antigen recognition pattern of L₃T₄ T-cells clones from Mycobacterium tuberculosis immune mice. Infect. Immun., 54: 291-296, 1986.

[15] 15. KAUFMANN, S.H.E.; VATH, V.; THOLE, J.E.R.; VAN EMBDEN, J.D.A. & EMMRICH, F. Enumeration of T cells reactive with Mycobacterium tuberculosis organisms and specific for the recombinant mycobacterial 64-KDa protein. Europ. J. Immunol., 17: 351-357, 1987.

[16] 16. KAUFMANN, S.H.E. - In vitro analysis of the cellular mechanisms involved in immunity to tuberculosis. Rev. infect. Dis., 11 (Suppl. 2): S448-S459, 1989.

[17] 17. KLEINHENZ, M.E. & ELLNER, J.J. Antigen responsiveness during tuberculosis: regulatory interactions of T cell subpopulations and adherent cells. J. Lab. clin. Med., 110: 31-40, 1987.

[18] 18. LAMB, J.R.; IVANYI, J.; REES, A.; YOUNG, R.A. & YOUNG, A.B. - The identification of T cells, epitopes in Mycobacterium tuberculosis using human T lymphocyte clones. Leprosy Rev., 57: 131-137, 1986.

[19] 19. LIMAMBUL, S.; SHORE, A.; DOSCH, N.M. & GELFAND, W. Theophylline modulation of E rosette formations: an indicator of T-cell maturation. Clin. exp. Immunol., 33: 503-508, 1978.

[20] 20. MÜLLER, I.; COBBOLD, S.P.; WALDMAN, H. & KAUFMANN, S.H.E. Impaired resistance to Mycobacterium tuberculosis infection after selective in-vivo depletion of L₃T₄ and Lyt2⁺ T cells. Infect. Immun., 55: 2037-2041, 1987.

[21] 21. OFTUNG, F.; MUSTAFA, A.S.; HUSSON, R.A. & GODAL, T. Human T cell clones recognize two abundant Mycobacterium tuberculosis protein antigens expressed in Escherichia coli. J. Immunol., 138: 927-931, 1987.

[22] 22. ORME, I.A. & COLLINS, F.M. Adoptive protection of Mycobacterium tuberculosis infected lung: dissociation between cells that passively transfer protective immunity and those that transfer delayed-type hipersensitivity to tuberculin. Cell. Immunol., 84: 113-120, 1984.

[23] 23. ORME, I.M. The kinetics of emergence and loss of mediator T lymphocytes acquired in response to infection with Mycobacterium tuberculosis. J. Immunol., 138: 293-298, 1987.

[24] 24. PIESSENS, W.F. Introduction to the immunology of tuberculosis. Rev. infect. Dis., 11 (Suppl. 2): S436-S441, 1989.

[25] 25. ROOK, G.A.W. Role of activated macrophages in the immunology of tuberculosis. Brit. med. Bull., 44: 611-623, 1988.

[26] 26. ROOK, G.A.W.; CARSWELL, J.W. & STANFORD, J.J. Preliminary evidence for trapping of antigen specific lymphocytes in the lymphoid tissue of anergic tuberculosis patients. Clin. exp. Immunol., 26: 129-132, 1976.

[27] 27. SHOAT, B. & JOSHNA, H. Supressor helper and immu-noregulatory T cells in normal human blood as defined by theophylline sensitivity. Thymus, 4: 323, 1982.

[28] 28. SMITH, D.W. & WEIEGESHAUS, E.H. - What animal models can teach us about the pathogenesis of tuberculosis in man. Rev. infect. Dis., 11 (Suppl. 2): S385-S393, 1989.

[29] 29. STEEL, J.; FLINT, K.C.; POZNICK, A.L.; HUDSPITH, B.; JOHNSON, M.M. & ROOK, G.A.W. Inhibition of virulent Mycobacteria tuberculosis by murine peritoneal macrophages and human alveolar lavage cells. The effect of lymphokines and recombinant gamma interferon. Tubercle, 67: 289-294, 1986.

[30] 30. VRIES, R.R.P. Regulation of T cell responsiveness against mycobacterial antigens by HLA class 2 immune response genes. Rev. infect. Dis., 11 (Suppl. 2): S400-S403, 1989.

[31] 31. WYBRAM, J. The human rosette forming cells as a marker of a population of thymus derived cells. J. clin. Invest., 51: 2537-2545, 1972.

[32] 32. WYBRAM, J. Rosette forming cells in immunologic defficience diseases and transferfactor. New Engl. J. Med., 281: 710-716, 1973.

Brasil

Brasil

Evaluación de las subpoblaciones de linfocitos T en pacientes tuberculosos empleand la modulación con teofilina

T lymphocyte subsets evaluation in patients with pulmonary tuberculosis using theophylline modulation

Resúmenes

Dirección para la Correspondencia:

Fechas de Publicación

Histórico