Fully immunocompetent CD8+ T lymphocytes are present in autologous haematopoietic stem cell transplantation recipients despite an ineffectual T-helper response.
BACKGROUND
Reduced CD4 T lymphocytes counts can be observed in HIV infection and in patients undergoing autologous haematopoietic stem cell transplantation (ASCT). Nevertheless, whereas opportunistic infections (OI) are frequent in HIV-infected individuals with low cell counts, OI are uncommon in ASCT patients.


RESULTS
To verify whether this observation could be secondary to intrinsic HIV-correlated T cell defects, we performed in-depth immunologic analyses in 10 patients with comparable CD4 counts in whom lymphopenia was secondary either to HIV-infection or ASCT-associated immunosuppressive therapy and compared them to age-matched healthy subjects. Results showed the presence of profound alterations in CD4+ T lymphocytes in both groups of patients with respect to healthy controls. Thus, a low percentage of CCR7+ CD4+ T cells and a compensative expansion of CD45RA-CCR7- CD4+ T cells, a reduced IL-2/IFN-gamma cytokine production and impaired recall antigens-specific proliferative responses were detected both in ASCT and HIV patients. In stark contrast, profound differences were detected in CD8+ T-cells between the two groups of patients. Thus, mature CD8+ T cell prevailed in ASCT patients in whom significantly lower CD45RA-CCR7- cells, higher CD45RA+CCR7- CD8+ cells, and an expansion of CCR7+CD8+ cells was detected; this resulted in higher IFN-gamma +/TNFalpha production and granzyme CD8+ expression. The presence of strong CD8 T cells mediated immune responses justifies the more favorable clinical outcome of ASCT compared to HIV patients.


CONCLUSIONS
These results indicate that CD8 T cells maturation and functions can be observed even in the face of a profound impairment of CD4+ T lymphocytes in ASCT but not in HIV patients. Primary HIV-associated CD8 defects or an imprinting by an intact CD4 T cell system in ASCT could justify these results.
Bandera
Alessandra
A
Division of Infectious Diseases, Department of Internal Medicine, "San Gerardo" Hospital, University of Milan-Bicocca, Monza, Italy. a.bandera@hsgerardo.org
Trabattoni
Daria
D
Pacei
Michela
M
Fasano
Francesca
F
Suardi
Elisa
E
Cesari
Miriam
M
Marchetti
Giulia
G
Pogliani
Enrico M
EM
Franzetti
Fabio
F
Clerici
Mario
M
Gori
Andrea
A
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000502:physiology; D016022:Case-Control Studies; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D003430:Cross-Sectional Studies; D015658:HIV Infections / Q000276:immunology / Q000473:pathology; D015497:HIV-1; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007121:Immunocompetence / Q000502:physiology*; D008875:Middle Aged; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014181:Transplantation Immunology / Q000502:physiology*; D014182:Transplantation, Autologous