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-Producing Lymphocytes Is a Manifestation of Immunologic Memory and Correlates with the Risk of Posttransplant Rejection Episodes
,§
Departments of
*
Medicine,
Pathology, and
Surgery and
§
Histocompatibility Laboratory, University Hospitals of Cleveland, Cleveland Veterans Affairs Medical Center and Case Western Reserve University, Cleveland, OH, 44106
While matching for MHC Ags improves renal allograft survival,
closely matched grafts sometimes fail due to rejection, and poorly
matched allografts are often well tolerated by the recipient. The
severity of the rejection process may partially depend on the presence
of environmentally primed T cells in the recipient that cross-react
with donor Ags. To test for the presence of primed, donor-specific T
cells in humans before transplantation, we used an enzyme-linked
immunospot assay for detection of allospecific cytokines produced by
individual human PBLs. We demonstrate that this approach detects
cytokine production at single cell resolution and detects production of
IFN-
only when there is defined immunologic priming, thus
representing a measure of primed donor-specific immunity. Because the
environmental Ag exposure of the recipient is not a function of the HLA
mismatch between donor and potential recipient, the number of HLA
mismatches may not correlate with the frequency of pretransplant,
donor-specific IFN--producing PBLs. Studies of donor-specific
IFN--producing lymphocytes in a cohort of patients being evaluated
for renal transplantation corroborated this hypothesis. Moreover, for
recipients of both living and cadaver renal allografts, the
pretransplant frequency of donor-specific memory cells correlated with
the posttransplant risk of developing acute rejection episodes. This
improved ability to define the strength of the allospecific immune
response by enzyme-linked immunospot assay may allow improved pairing
of recipients with donors and identification of kidney allograft
donor-recipient pairs at high risk for acute rejection, thus permitting
targeted interventions aimed at prolonging graft
survival.
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N. Najafian, A. D. Salama, E. V. Fedoseyeva, G. Benichou, and M. H. Sayegh Enzyme-Linked Immunosorbent Spot Assay Analysis of Peripheral Blood Lymphocyte Reactivity to Donor HLA-DR Peptides: Potential Novel Assay for Prediction of Outcomes for Renal Transplant Recipients J. Am. Soc. Nephrol., January 1, 2002; 13(1): 252 - 259. [Abstract] [Full Text] [PDF]
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P. S. Heeger and D. Hricik Immune Monitoring in Kidney Transplant Recipients Revisited J. Am. Soc. Nephrol., January 1, 2002; 13(1): 288 - 290. [Full Text] [PDF]
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R. J. Baker, M. P. Hernandez-Fuentes, P. A. Brookes, A. N. Chaudhry, H. T. Cook, and R. I. Lechler Loss of Direct and Maintenance of Indirect Alloresponses in Renal Allograft Recipients: Implications for the Pathogenesis of Chronic Allograft Nephropathy J. Immunol., December 15, 2001; 167(12): 7199 - 7206. [Abstract] [Full Text] [PDF]
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M. D. Hesse, A. Y. Karulin, B. O. Boehm, P. V. Lehmann, and M. Tary-Lehmann A T Cell Clone's Avidity Is a Function of Its Activation State J. Immunol., August 1, 2001; 167(3): 1353 - 1361. [Abstract] [Full Text] [PDF]
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P. S. Heeger, A. Valujskikh, and P. V. Lehmann23 Comprehensive Assessment of Determinant Specificity, Frequency, and Cytokine Signature of the Primed CD8 Cell Repertoire Induced by a Minor Transplantation Antigen J. Immunol., August 1, 2000; 165(3): 1278 - 1284. [Abstract] [Full Text] [PDF]
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S. K. Schwander, M. Torres, C. Carranza C, D. Escobedo, M. Tary-Lehmann, P. Anderson, Z. Toossi, J. J. Ellner, E. A. Rich, and E. Sada Pulmonary Mononuclear Cell Responses to Antigens of Mycobacterium tuberculosis in Healthy Household Contacts of Patients with Active Tuberculosis and Healthy Controls from the Community J. Immunol., August 1, 2000; 165(3): 1479 - 1485. [Abstract] [Full Text] [PDF]
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C. V. Hartig, G. W. Haller, D. H. Sachs, S. Kuhlenschmidt, and P. S. Heeger Naturally Developing Memory T Cell Xenoreactivity to Swine Antigens in Human Peripheral Blood Lymphocytes J. Immunol., March 1, 2000; 164(5): 2790 - 2796. [Abstract] [Full Text] [PDF]
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