Heat shock protein-induced T-lymphocyte propagation from endomyocardial biopsies in heart transplantation.
BACKGROUND
Recent studies have shown that heat shock proteins can be recognized by T cells during various immunologically mediated inflammatory processes. Injurious stimuli to cells induce an increased production of heat shock proteins which could lead to their cell surface expression and subsequent recognition by the immune system. We have postulated that allograft infiltrating cells may recognize heat shock proteins, especially during rejection.


METHODS
This hypothesis was tested by incubating heart transplant biopsy specimens from 89 heart transplant recipients with soluble Mycobacterium tuberculosis extracts, a source of heat shock proteins or recombinant mycobacterial heat shock protein 65. T cell phenotypes were determined by flow cytometry.


RESULTS
Mycobacterium tuberculosis extract can induce lymphocyte propagation from heart transplant biopsy specimens especially during rejection. A highly significant correlation was seen between Mycobacterium tuberculosis extract and interleukin-2-induced lymphocyte growth and an accelerated growth was seen for cultures incubated with Mycobacterium tuberculosis extract + interleukin-2. A second series of experiments has also shown the propagation of lymphocytes induced by recombinant mycobacterial heat shock protein-65. T-cell phenotype analysis of biopsy propagated lymphocytes has shown higher frequencies of CD8 cells in Mycobacterium tuberculosis extract and heat shock protein-65 propagated lymphocytes from early posttransplantation biopsy specimens, whereas, later on, most cultures showed a predominance of CD4 cells. T-cell receptor gamma delta cells were more frequently found in biopsy-derived lymphocyte cultures from long-term survivors, especially after propagation with Mycobacterium tuberculosis extract and heat shock protein-65. These gamma delta cells expressed primarily the delta 1 rather than the gamma 9 phenotype.


CONCLUSIONS
These observations provide first evidence for the presence of heat shock protein-reactive lymphocytes in cellular infiltrates of transplants undergoing rejection.
Moliterno
R
R
Division of Transplantation Pathology, University of Pittsburgh Medical Center, PA 15261, USA.
Woan
M
M
Bentlejewski
C
C
Qian
J
J
Zeevi
A
A
Pham
S
S
Griffith
B P
BP
Duquesnoy
R J
RJ
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology; D002478:Cells, Cultured; D004699:Endocardium / Q000473:pathology*; D005434:Flow Cytometry; D016027:Heart Transplantation / Q000276:immunology / Q000473:pathology*; D006360:Heat-Shock Proteins / Q000494:pharmacology*; D006801:Humans; D016130:Immunophenotyping; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000494:pharmacology; D009169:Mycobacterium tuberculosis; D009206:Myocardium / Q000473:pathology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000502:physiology*
D006360:Heat-Shock Proteins; D007376:Interleukin-2; D016692:Receptors, Antigen, T-Cell, gamma-delta; D011994:Recombinant Proteins