RATIONALE: Healthy household contacts (HHCs) of patients with active pulmonary tuberculosis are exposed aerogenically to Mycobacterium tuberculosis (Mtb), thus permitting the study of protective local immunity. OBJECTIVES: To assess alveolar macrophage (AM) and autologous blood CD4 and CD8 T-cell-mediated Mtb growth control in HHCs and healthy, unexposed community control subjects (CCs). METHODS: AMs were infected with Mtb strains H(37)Ra and H(37)Rv at multiplicities of infection 0.1 and 1. Mtb colony-forming units were evaluated on Days 1, 4, and 7. MAIN RESULTS: CD8 T cells from HHCs in 1:1 cocultures with AMs significantly (p < 0.05) increased Mtb growth control by AMs. In CCs, no detectable contribution of CD8 T cells to Mtb growth control was observed. CD4 T cells did not increase Mtb growth control in HHCs or in CCs. IFN-gamma, nitric oxide, and tumor necrosis factor were determined as potential mediators of Mtb growth control in AMs and AM/CD8 and AM/CD4 cocultures. IFN-gamma production in AM/CD4 was twofold higher than that in AM/CD8 cocultures in both HHCs and CCs (p < 0.05). Nitric oxide production from AMs of HHCs increased on Days 4 and 7 and was undetectable in AMs from CCs. IFN-gamma and nitric acid concentrations and Mtb growth control were not correlated. Tumor necrosis factor levels were significantly increased in AM/CD8 cocultures from HHCs compared with AM/CD8 cocultures from CCs (p < 0.05). CONCLUSION: Aerogenic exposure to Mtb in HHCs leads to expansion of Mtb-specific effector CD8 T cells that limit Mtb growth in autologous AMs.
RATIONALE: Healthy household contacts (HHCs) of patients with active pulmonary tuberculosis are exposed aerogenically to Mycobacterium tuberculosis (Mtb), thus permitting the study of protective local immunity. OBJECTIVES: To assess alveolar macrophage (AM) and autologous blood CD4 and CD8 T-cell-mediated Mtb growth control in HHCs and healthy, unexposed community control subjects (CCs). METHODS: AMs were infected with Mtb strains H(37)Ra and H(37)Rv at multiplicities of infection 0.1 and 1. Mtb colony-forming units were evaluated on Days 1, 4, and 7. MAIN RESULTS:CD8 T cells from HHCs in 1:1 cocultures with AMs significantly (p < 0.05) increased Mtb growth control by AMs. In CCs, no detectable contribution of CD8 T cells to Mtb growth control was observed. CD4 T cells did not increase Mtb growth control in HHCs or in CCs. IFN-gamma, nitric oxide, and tumor necrosis factor were determined as potential mediators of Mtb growth control in AMs and AM/CD8 and AM/CD4 cocultures. IFN-gamma production in AM/CD4 was twofold higher than that in AM/CD8 cocultures in both HHCs and CCs (p < 0.05). Nitric oxide production from AMs of HHCs increased on Days 4 and 7 and was undetectable in AMs from CCs. IFN-gamma and nitric acid concentrations and Mtb growth control were not correlated. Tumor necrosis factor levels were significantly increased in AM/CD8 cocultures from HHCs compared with AM/CD8 cocultures from CCs (p < 0.05). CONCLUSION: Aerogenic exposure to Mtb in HHCs leads to expansion of Mtb-specific effector CD8 T cells that limit Mtb growth in autologous AMs.
Authors: Deborah A Lewinsohn; Amy S Heinzel; James M Gardner; Liqing Zhu; Mark R Alderson; David M Lewinsohn Journal: Am J Respir Crit Care Med Date: 2003-09-11 Impact factor: 21.405
Authors: S K Schwander; M Torres; C Carranza C; D Escobedo; M Tary-Lehmann; P Anderson; Z Toossi; J J Ellner; E A Rich; E Sada Journal: J Immunol Date: 2000-08-01 Impact factor: 5.422
Authors: E Jouanguy; S Lamhamedi-Cherradi; F Altare; M C Fondanèche; D Tuerlinckx; S Blanche; J F Emile; J L Gaillard; R Schreiber; M Levin; A Fischer; C Hivroz; J L Casanova Journal: J Clin Invest Date: 1997-12-01 Impact factor: 14.808
Authors: S Cho; V Mehra; S Thoma-Uszynski; S Stenger; N Serbina; R J Mazzaccaro; J L Flynn; P F Barnes; S Southwood; E Celis; B R Bloom; R L Modlin; A Sette Journal: Proc Natl Acad Sci U S A Date: 2000-10-24 Impact factor: 11.205
Authors: Jussi J Saukkonen; Beth Bazydlo; Michael Thomas; Robert M Strieter; Joseph Keane; Hardy Kornfeld Journal: Infect Immun Date: 2002-04 Impact factor: 3.441
Authors: S K Schwander; M Torres; E Sada; C Carranza; E Ramos; M Tary-Lehmann; R S Wallis; J Sierra; E A Rich Journal: J Infect Dis Date: 1998-11 Impact factor: 5.226
Authors: Kerry J Welsh; Shen-An Hwang; Sydney Boyd; Marian L Kruzel; Robert L Hunter; Jeffrey K Actor Journal: Tuberculosis (Edinb) Date: 2011-12-03 Impact factor: 3.131
Authors: Srijata Sarkar; Youngmia Song; Somak Sarkar; Howard M Kipen; Robert J Laumbach; Junfeng Zhang; Pamela A Ohman Strickland; Carol R Gardner; Stephan Schwander Journal: J Immunol Date: 2012-02-15 Impact factor: 5.422
Authors: Martha Torres; Claudia Carranza; Srijata Sarkar; Yolanda Gonzalez; Alvaro Osornio Vargas; Kathleen Black; Qingyu Meng; Raul Quintana-Belmares; Martha Hernandez; Jose Juan F Angeles Garcia; Victor Hugo Páramo-Figueroa; Marco Antonio Iñiguez-Garcia; Jose L Flores; Junfeng Jim Zhang; Carol R Gardner; Pamela Ohman-Strickland; Stephan Schwander Journal: Thorax Date: 2019-04-29 Impact factor: 9.139