Zhanzhuo Li

• MD, PhD
• Researcher at National Institute of Allergy and Infectious Diseases, National Institutes of Health

The ability to successfully transplant cells and organs from a donor into an immunologically disparate recipient is one of the greatest treatment advances in the history of medicine. Nevertheless, acute and chronic rejection, graft versus host disease, and the inability to identify suitable donors continue to be challenges and limit broader applica...

Hematopoietic chimerism after allogeneic bone marrow transplantation may establish a state of donor antigen-specific tolerance. However, current allotransplantation protocols involve genotoxic conditioning which has harmful side-effects and predisposes to infection and cancer. Here we describe a non-genotoxic conditioning protocol for fully MHC-mis...

WHIM-09 is the first patient described with WHIM syndrome, an autosomal dominant form of neutropenia related to bone marrow retention of neutrophils. Originally diagnosed incorrectly with autoimmune neutropenia, the patient underwent splenectomy at age 9, but the absolute neutrophil count (ANC) did not rise. Subsequently, she was spontaneously cure...

Patient WHIM-09 was cured of WHIM syndrome, an autosomal dominant immunodeficiency disorder caused by gain-of-function CXCR4 mutations, by chromothripsis (chromosome shattering) in a single hematopoietic stem cell (HSC). Chromothripsis fortuitously deleted CXCR4WHIM, and one copy of 163 other genes, resulting in hematopoietic chimerism (100% chromo...

Hematopoietic chimerism is known to promote donor-specific organ allograft tolerance; however, clinical translation has been impeded by the requirement for toxic immunosuppression and large doses of donor bone marrow (BM) cells. Here, we investigated in mice whether durable chimerism might be enhanced by pre-treatment of the recipient with liposoma...

Hematopoietic chimerism established by allogeneic bone marrow transplantation is known to promote donor-specific organ allograft tolerance; however, clinical application is limited by the need for toxic host conditioning and "megadoses" of donor bone marrow cells. A potential solution to this problem has been suggested by the observation that recip...

AMD3100 (plerixafor), is a specific CXCR4 antagonist approved by the FDA for mobilizing hematopoietic stem cells from bone marrow to blood for transplantation in cancer. AMD3100 also mobilizes most mature leukocyte subsets to blood; however, their source and trafficking potential have not been fully delineated. Here, we show that a single injection...

The clinical practice of vascularized composite allotransplantation (VCA) has been limited by the potential side effects of chronic immunosuppression. Studies using rodent models have been useful for dissecting mechanisms underlying immunological events induced by VCA and for developing protocols such as mixed chimerism for tolerance induction. Mou...

AMD3100 is approved for mobilizing hematopoietic stem cells to blood for transplantation in cancer by blocking chemokine receptor CXCR4. It also mobilizes mature leukocytes to blood; however, there is conflicting published evidence regarding the source of mobilized neutrophils (bone marrow vs lung), and the source(s) of other mobilized leukocytes i...

CXCR4 and its chemokine ligand, CXCL12, have been implicated in directing the migration of primordial germ cells during organogenesis and are responsible for the retention of hematopoietic cells in bone marrow. Although CXCR4 was found to be expressed in normal human adrenal cortex (and not in the medulla), its role in adrenal physiology and diseas...

The growing development of composite tissue allografts (CTA) highlights the need for tolerance induction protocols. Herein, we developed a mouse model of heterotopic limb allograft in a stringent strain combination in which potentially tolerogenic strategies were tested taking advantage of donor stem cells in the grafted limb. BALB/c allografts wer...

We developed a mouse model of heterotopic limb transplantation in which we took advantage of Thy1.1 and Thy1.2 congenic strains to track and characterize donor T cells, to determine the role of recipient's thymus in mixed T-cell chimerism induction as well as transplant immunocompetence. The vascularized Thy1.1 limb graft composed of femur, muscle,...

We studied the gene expression in rat cardiac allografts retransplanted into (donor x recipient) F1 animals to identify unknown or unexpected genes whose expression might contribute to the progression of transplant vasculopathy. Gene expression was first studied using a mRNA differential display, then it was further investigated using quantitative...

Chemokine systems probably play a role in transplant vasculopathy; however, a comprehensive study of the expression of chemokines and their receptors in this disease has not been performed. The expression of all the rat chemokines and chemokine receptor genes for which the nucleotide sequences are known were quantitatively monitored using the fluor...

A precise understanding of immunological mechanisms is needed to prevent transplant vasculopathy. The developing process of transplant vasculopathy was investigated by retransplanting rat cardiac allografts and measuring the expressions of 21 different genes inside the retransplanted allografts under nonimmunosuppressive conditions. Significant tra...

Chronic allograft vasculopathy (CAV) is caused by the infiltration of host immune cells to a graft, but it has been technically difficult to monitor the movements of the cells in graft rejection. We used a male-specific gene, SRY, as a marker to investigate the dynamics of host cells in a model of CAV in which immunosuppression was unnecessary and...