Factors involved in the generation of memory CD8+ T cells in patients with X-linked lymphoproliferative disease (XLP)

Abstract

SummaryWe have analysed the phenotype of T lymphocytes in two X-linked lymphoproliferative disease (XLP) patients with the same SH2D1A mutation differing in initial exposure to Epstein-Barr virus (EBV) and treatment. While memory T lymphocytes (with low CCR7 and CD62L expression) prevailed in both XLP patients, in patient 9, who developed acute infectious mononucleosis (AIM) and received B cell ablative treatment, the predominant phenotype was that of late effector CD8 T cells (CD27 -, CD28 -, CCR7 -, CD62L -, CD45 RA + , perforin + ), while in patient 4 (who did not suffer AIM) the prevalent phenotype of CD8 T lymphocytes was similar to that of normal controls (N) or to that of adult individuals who recovered from AIM: CD27 + , CD28 + , CCR7 -, CD62L -, CD45 RO + and perforin -. CD57 expression (related to senescence) was also higher in CD8 T cells from patient 9 than in patient 4, AIM or N. Persistently high EBV viral load was observed in patient 9. The results obtained from this limited number of XLP patients suggest that events related to the initial EBV encounter (antigen load, treatment, cytokine environment) may have more weight than lack of SH2D1A in determining the long-term differentiation pattern of CD8 memory T cells.

Increased lymphocyte viability after non-stimulated peripheral blood mononuclear cell (PBMC) culture in patients with X-linked lymphoproliferative disease (XLP)

“…Along the studies designed to analyze the development of memory T and B lymphocytes in adult XLP patients [5], we observed a survival advantage for XLP lymphocytes after culture. Because this fact could be related to lymphocyte immortalization and transformation leading to malignancy, we have studied cell viability and the phenotypic characteristics of XLP lymphocytes that survive in vitro after nonstimulated culture [6].…”

“…Our results indicate that survival of memory CD8 T lymphocytes was higher in XLP patients compared to normal controls (N). After 30 days the surviving memory CD8 T cells in XLP cultures corresponded to those with high IFNγ and low perforin [5]. Regarding B lymphocytes, while at the beginning of the culture B cells with a naïve phenotype predominated in XLP, mainly B cells with a memory CD27+, IgD+, IgM+ phenotype [7] prevailed in XLP after 30 days of culture.…”

Severe haemophilia A patients have reduced numbers of peripheral memory B cells

“…It has been reported that CD70 can deliver co‐stimulatory signals in cognate T–B interactions [13] through interaction with CD27 present in T lymphocytes. Moreover, CD70+ B lymphocytes are necessary to provide signals for the retention of CD27 on viral specific memory CD8+ T lymphocytes [14,15].…”

Progressive reduction of circulating B lymphocytes in patients with X‐linked lymphoproliferative disease (XLP)

“…Inefficient immune response against EBV is unable to control EBV expansion in most cases. Abnormalities in the balance of T helper 1 (Th1)/Th2 responses and accumulation of activated CD8 + T lymphocytes have been described (Czar et al, 2001;Belmonte et al, 2007). The percentage of memory B cells (CD27 + B lymphocytes) in B lympocytes is reduced in XLP patients surviving primary EBV infection compared to that of normal controls (Malbran et al, 2001).…”

“…The older sibling (Patient four) developed XLP-related hypogammaglobulinaemia after a tonsilar lymphoma when 4 years old, and remained on gamma globulin treatment for 35 years. (Belmonte et al, 2007).…”