Host natural killer immunity is a key indicator of permissiveness for donor cell engraftment in patients with severe combined immunodeficiency

Abstract

BackgroundSevere combined immunodeficiency (SCID) can be cured by using allogeneic hematopoietic stem cell transplantation, and the absence of host immunity often obviates the need for preconditioning. Depending on the underlying genetic defect and when blocks in differentiation occur during lymphocyte ontogeny, infants with SCID have absent or greatly reduced numbers of functional T cells. Natural killer (NK) cell populations are usually absent in the SCID-X1 and Janus kinase 3 forms of SCID and greatly reduced in adenosine deaminase deficiency SCID but often present in other forms of the disorder.ObjectiveTo determine if SCID phenotypes indicate host permissiveness to donor cell engraftment.MethodsA retrospective data analysis considered whether host NK cells influenced donor T-cell engraftment, immune reconstitution, and long-term outcomes in children who had undergone nonconditioned allogeneic stem cell transplantation between 1990 and 2011 in the United Kingdom. Detailed analysis of T- and B-cell immune reconstitution and donor chimerism was compared between the NK+ (n = 24) and NK− (n = 53) forms of SCID.ResultsOverall, 77 children underwent transplantation, with survival of 90% in matched sibling donor/matched family donor transplants compared with 60% when alternative donors were used. Infants with NK−SCID were more likely to survive than NK+ recipients (87% vs 62%, P < .01) and had high-level donor T-cell chimerism with superior long-term recovery of CD4 T-cell immunity. Notably, 33% of children with NK+SCID required additional transplantation procedures compared with only 8% of children with NK−SCID (P < .005).ConclusionsNK−SCID disorders are highly permissive for donor T-cell engraftment without preconditioning, whereas the presence of NK cells is a strong indicator that preparative conditioning is required for engraftment of T-cell precursors capable of supporting robust T-cell reconstitution.

Insufficient immune reconstitution after allogeneic cord blood transplantation without chemotherapy conditioning in patients with SCID caused by CD3δ deficiency

“…Therefore, it is possible that the T-precursor niche is occupied by the recipient cells, which might result in the competition during the process of donor T-cell maturation. Our results are in line with the report by Hassan et al, 14 which indicated that NK + SCID was less permissive for donor T-cell engraftment and the peripheral blood T-cell numbers were significantly lower in NK + SCID patients than in NK − SCID patients after HSCT without conditioning. They suggested that the thymus with recipient T-cell precursors might affect the process of T-cell reconstitution after HCST without conditioning.…”

SCID pigs: An emerging large animal NK model

“…NK-type SCID individuals have enhanced survival with allogeneic stem cell transplantations compared with NK+ SCID patients 26 , while the presence or absence of B cells did not impact success in such patients. In addition, 33% of NK+ SCID stem cell recipients required additional procedures, including pretransplant myeloablation and/or radiation, while only 8% of NK-recipients required such procedures 26 .…”

Donor Chimerism in Patients With Primary Immunodeficiency After Allogeneic Hematopoietic Stem Cells Transplantation

“…ТКИН характеризуются глубокой Т-клеточной лимфопенией или олигоклональными нефункцио-нальнымиТ-клетками(нарушениеТ-клеточнойдиф-ференцировки),какприОмен-синдроме.Отсутствие Т-клеточного иммунитета, а также В-и ЕК-клеток принекоторыхТКИНпредставляетсобойуникальное условиедляприживлениядонорскихклетокиопреде-ляет выбор режима кондиционирования (чаще ис-пользуютRICилитрансплантациюбезкондициони-рования) [2,14,22]. Во многих исследованиях, как ивнашем,показано,чтоупациентовсТКИНсубпо-пуляцияТ-лимфоцитовчащедонорскаядажеприот-сутствии кондиционирования [17,18,23,24], а для приживлениядонорскихмиелоидныхиВ-клетокпри В+ТКИНнеобходимопроведениеподготовительно-горежимапередаллоТГСК [18,[23][24][25][26].…”