Peripheral lymph node helper T-cell recovery after syngeneic bone marrow transplantation in mice prepared with either gamma-irradiation or busulfan

Abstract

The optimum marrow ablative regimen for preparing recipients of bone marrow transplantation (BMT) has not been established. gamma- Irradiation, but not busulfan, produces a characteristic microvascular injury pattern which results in depressed capacity of normal lymphocytes to localize into the lymph nodes of syngeneic murine BMT recipients. Since peripheral lymph nodes are important sites for initiation and amplification of immune responses, the preparative regimen might delay recovery of regionally compartmentalized immune functions after BMT. We evaluated the effects of busulfan and gamma- irradiation on the phenotypic and functional reconstitution of helper T- cell function within the peripheral lymph nodes of BMT recipients. Both marrow ablative regimens caused a protracted delay in regeneration of peripheral lymph node CD4+ T cells. Specific helper T-cell functions, such as contact hypersensitivity and alloantigen responses, remained significantly depressed in the lymph nodes of irradiated mice for prolonged periods (up to 60 weeks). These responses recovered more rapidly in busulfan-treated BMT recipients. In contrast, the capacity of peripheral lymph node T cells to provide “help” for antigen-specific immunoglobulin production was only transiently depressed by either preparative regimen. Our experiments confirm the hypothesis that the marrow ablative regimen, particularly gamma-irradiation, may contribute to the period of immunodeficiency which follows BMT. The pattern of immune recovery observed suggests that preparative total body irradiation (TBI) may selectively depress the regional recovery of the TH1 [interleukin-2 (IL-2) and gamma-interferon (gamma-IFN) secreting] lymphocyte subset.

Differences in Aspergillus‐specific immune recovery between T‐cell‐replete and T‐cell‐depleted hematopoietic transplants

“…This finding was surprising because immune reconstitution is usually better in pediatric patients in whom thymic function persists, unlike adults . Furthermore, in adults, conditioning‐induced tissue damage prevents memory T‐cell homing to and regeneration in peripheral lymphoid tissues and naïve T‐cell production starts months after transplantation. Crucial factors in the onset of IA are neutropenia soon after HSCT, delayed T‐cell immune recovery from the second–third month post‐transplant onwards (late IA) or after day +100 (very late IA) steroid‐based treatment of GvHD .…”

Busulfan-conditioned bone marrow transplantation results in high-level allogeneic chimerism in mice made tolerant by in utero hematopoietic cell transplantation

“…DLI was unable to enhance chimerism in mice with levels of donor cell engraftment less than 1% following IUHCT [17] and carries the potential risk of GVHD. TBI is known to induce a proin-flammatory cytokine response and is associated with microvascular injury [25]. More importantly, the use of low-dose TBI in clinical settings, especially in pediatrics, has been associated with the development of iatrogenic cancers and cataracts [26][27][28].…”

Thymosin α1 to harness immunity to pathogens after haploidentical hematopoietic transplantation

“…For up to 1 year after transplant, early immune recovery in adults with their decayed thymic function, 40–43 stems from expansion of mature T cells in the graft 40–44 . Naïve T cells are produced months after transplantation because conditioning‐induced tissue damage prevents T cell homing to peripheral lymphoid tissues, 45,46 where T cell memory is generated and maintained 47 . After about 1 year post‐transplant life‐threatening episodes rarely occurred, confirming that immunological reconstitution was practically complete by this stage 28–31 .…”