Introduction:

Cell-mediated immune (CMI) responses including CD4+ and CD8+ T-cells contribute to control of Mycobacterium tuberculosis (MTb) infection. There are no data on long term TB-specific CMI in solid organ transplant (SOT) patients after treatment of active TB. We determined MTb-specific cellular immunity in a cross-sectional study of SOT patients that had previously had active tuberculosis.

Methods:

Adult SOT patients previously treated for microbiologically-proven active TB were identified at a large transplant center in a low TB prevalence area. Whole blood was collected for QuantiFERON-TB (QFT) and flow-cytometry based CMI testing. For flow cytometry, peripheral blood mononuclear cells were stimulated with recombinant MTb antigens ESAT6 and CFP10. Flow cytometry was used to characterize MTb-specific IFN-γ-producing CD4⁺ and CD8⁺ central memory (T_CM, CD45RA^–, CCR7⁺), effector memory (T_EM CD45RA^–, CCR7^–) and terminally-differentiated effector memory RA T-cells (T_EMRA CD45RA⁺, CCR7^–).

Results:

Of 31 patients who developed active TB from 2002-2015, 8 provided samples for analysis. Types of transplant were kidney (n=3), liver (n=3), and lung (n=2); median time from TB diagnosis was 4.83 years (range 1.25-10.7). QFT results ranged from 0.16-83.5 IU/mL and 7/8 patients had MTb-specific IFN-γ-producing T-cells. Frequencies of MTb-specific IFN-γ producing CD4⁺ and CD8⁺ T-cells ranged from 0.0-6.97% and 0.0-16.47%, respectively. Effector memory T-cells (T_EM) were the most frequent subtype of TB-specific CD4⁺ and CD8⁺ cells ranging from 0.0-4.72% and 0.0-5.46% respectively. In addition to T_EM phenotype, antigen-specific CD8⁺ T cells predominantly expressed a T_EMRA phenotype in contrast to the CD4⁺ T cells that expressed a T_CM phenotype. There was moderate correlation between QFT results and IFN-γ producing CD4 and CD8 T cells (Spearman rho 0.63, p=0.094). There was no association of T-cell response with extent of disease, time from diagnosis or current immunosuppression. However, the two lung transplant recipients had the lowest T-cell and QFT results.

Conclusion:

Our results suggest that the majority of SOT patients previously treated for TB demonstrate immune responses to TB in the long-term which may confer protection if they are re-exposed. Long term TB-specific CD4+ T-cell responses are primarily in the T_CM compartment, while CD8+ T-cells are predominantly of a terminally differentiated (T_EMRA) phenotype.

CITATION INFORMATION: Nellimarla S., Natori Y., Ferreira V., Husain S., Humar A., Kumar D. Characterization of Mycobacterium Tuberculosis Memory T Cell Subsets in Solid Organ Transplant Recipients with Previously Treated Active Tuberculosis Am J Transplant. 2017;17 (suppl 3).

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