Peripheral CD19+CD24^highCD38^high B-regulatory cells in lung transplant recipients

The role of CD19+CD24^highCD38^high B-regulatory cells in solid-organ Transplant (Tx) in acceptance are still scarce. In previous studies on kidney transplant recipients may suggest a protective role of this cell subtype in graft tolerance and the existence of a cross talk between B-and T-regulatory clones. In lung transplantation, the role of B-regulatory cells has never been investigated. In a murine tracheal transplantation model, this subset seems able to prevent tracheal obliteration when in combination with rapamycin. Aim of this study is to analyze peripheral CD19+CD24^highCD38^high B-reg cells counts in a cohort of lung recipients, their association with several clinical and pharmacological variables and their possible association with T regulatory cell.

From Jan 2009 to Dec 2014, 117 lung Tx recipients were submitted to an immunological follow up I-FU(median: 108.7 months (6.7-310.5)). Immunological follow up consisted of a complete blood peripheral immuno-phenotype, inclusive of CD19+CD24^highCD38^high B-cells (globally 1106 determinations). We tested the association between B-reg and relevant variables by linear or regression models for repeated measures, adjusting for time from Tx.

Among all variables analyzed at multivariate analysis: chronic rejection (OR - 0.19, p = .039), use of Mycophenolate (OR - 0.38, p < .001) and the presence of a concomitant pulmonary infection of S. aureus (OR 0.66, p = .002) and A. fumigatus (OR 0.50, p = .009) were significantly associated to B-reg cell. No significant correlation between CD19+CD24^highCD38^high B-reg cells and T-reg cells counts was found in our cohort.

Our present data highlight, for the first time, that this cell subset might participate in long-term lung graft acceptance mechanisms.