Reconstitution of naïve T cells and type 1 function after autologous peripheral stem cell transplantation: impact on the relapse of original cancer.
BACKGROUND
Phenotypic and functional reconstitution of T cells after peripheral blood stem cell transplantation (PBSCT) and its influence on posttransplant immune status is important in terms of immune surveillance and relapse of original cancer. We investigated the relationship between the dominant immune reconstitution pathway and the immune surveillance. We also tested the cytokine bias acquired by T cells after transplantation and its possible influence on relapse of original malignancy.


METHODS
Immunophenotyping of naïve and memory T cells was performed by flow cytometry on patients who underwent PBSCT for various cancers. Cytokine production by peripheral memory helper (CD4) and cytotoxic (CD8) T cells was investigated at various pretransplant and posttransplant time points with fluorescein isothiocyanate-based intracellular cytokine assay after short-term in vitro mitogenic stimulation (phorbol myristate acetate + ionomycin). Data on T-cell subsets and polarized cytokines gamma-interferon (Ifn) and interleukin 4 produced by memory T cells were compared with that of healthy controls.


RESULTS
The reconstitution of naïve T cells and gamma-Ifn-producing memory cells was significantly lower in patients who experienced relapse of original cancer within 1 year of PBSCT compared to those who showed no signs of relapse even after 2 years and compared to normal subjects. The results indicate that efficient reconstitution of naïve T cells and type 1 function of memory T cells are important in maintaining T-cell repertoire diversity after PBSCT. It also confers appropriate levels of immune surveillance against diverse neoantigens that evolve from residual tumor burden. The data reveal that chemotherapy-induced thymic injuries may impair regeneration of naïve cells that result in a naivopenic state in a susceptible host.


CONCLUSIONS
The study highlights the importance of naïve T-cell reconstitution and points towards cell replacement strategies for improving immune surveillance after PBSCT.
Mitra
D K
DK
Department of Histocompatibility and Immunogenetics and Medical Oncology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India.
Singh
H P
HP
Singh
M
M
Alwadi
A
A
Kochupillai
V
V
Raina
V
V
Kumar
L
L
Mehra
N K
NK
D000328:Adult; D015703:Antigens, CD / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation; D016207:Cytokines / Q000276:immunology; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D019337:Hematologic Neoplasms / Q000276:immunology / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis; D017493:Leukocyte Common Antigens / Q000032:analysis; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D012008:Recurrence; D012016:Reference Values; D013601:T-Lymphocytes / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D013997:Time Factors; D014182:Transplantation, Autologous / Q000276:immunology
D015703:Antigens, CD; D016207:Cytokines; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1