Beyond Self and Nonself: Fuzzy Recognition of the Immune System

Leng, Qibin; Bentwich, Zvi

doi:10.1046/j.1365-3083.2002.01105.x

Cited by 34 publications

(18 citation statements)

References 72 publications

(132 reference statements)

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“…However, with the realization that many self-reactive lymphocytes survive central and peripheral tolerance, this view has had to be modified [49]. Limited immune responses to self-antigens (autoimmunity) are now understood to be normal and not necessarily pathologic [63]. …”

Section: Immune Abnormalities In Autismmentioning

confidence: 99%

HLA Immune Function Genes in Autism

Torres

Westover

Rosenspire

2012

Autism Research and Treatment

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The human leukocyte antigen (HLA) genes on chromosome 6 are instrumental in many innate and adaptive immune responses. The HLA genes/haplotypes can also be involved in immune dysfunction and autoimmune diseases. It is now becoming apparent that many of the non-antigen-presenting HLA genes make significant contributions to autoimmune diseases. Interestingly, it has been reported that autism subjects often have associations with HLA genes/haplotypes, suggesting an underlying dysregulation of the immune system mediated by HLA genes. Genetic studies have only succeeded in identifying autism-causing genes in a small number of subjects suggesting that the genome has not been adequately interrogated. Close examination of the HLA region in autism has been relatively ignored, largely due to extraordinary genetic complexity. It is our proposition that genetic polymorphisms in the HLA region, especially in the non-antigen-presenting regions, may be important in the etiology of autism in certain subjects.

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Section: Immune Abnormalities In Autismmentioning

confidence: 99%

HLA Immune Function Genes in Autism

Torres

Westover

Rosenspire

2012

Autism Research and Treatment

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“…If so, the present study would suggest that the degeneracy of TCR recognition (6) does not extend to a cross-reactivity between the environmental antigens to which the donor's T cells have been primed and the miHAs on allogeneic tissues of the host in this model system. It is essential that the GVHD-inducing potential of CD44 + CD62L -CD4 + memory T cells be examined in a variety of other miHAand MHC-mismatched donor-host murine strain combinations.…”

Section: Figurementioning

confidence: 72%

Pleasant memories: remembering immune protection while forgetting about graft-versus-host disease

Sondel¹,

Buhtoiarov²,

DeSantes³

2003

J. Clin. Invest.

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In this issue of the JCI, Anderson et al. (5) report on the coinfusion of purified CD4 + memory T cells in an MHCmatched, miHA-disparate, T celldepleted murine HSCT model. Their results conclusively show that unpurified CD4 + T cells cause GVHD, while the memory cells (defined here as CD44 + -CD62L -CD4 + T cells) do not. Furthermore, memory CD4 + T cells taken from a donor immunized to chicken γ-globulin (CGG) retain their CGG-specific memory when the recipient of those memory T cells is immunized with CGG. In other words, these CD44 + -CD62L -CD4 + memory T cells remember how to respond to antigens to which they were primed but have "forgotten" how to react to allogeneic miHAs that are the targets of GVHD mediated by unfractionated or naive CD4 + T cells. Applicability to other strain combinationsThis finding provides some insight on the nature of alloreactivity. In this HSCT model, the CD4 + T cells responsible for GVHD are not in the CD44 + CD62L --CD4 + population (5). As such, the components of the T cell receptor (TCR) repertoire that recognize the miHAs may not be in the CD44 + CD62L -CD4 + mem- Clinical transplantation of hematopoietic stem cells (HSCs) was first successful in 1968 (1, 2) and has provided life-saving therapy for potentially fatal diseases. These include acquired marrow aplasia, inherited dysfunction of hematopoietically-derived elements, and the iatrogenic marrow failure caused by supra-lethal chemo-or radiotherapy in the treatment of neoplasms. The goal of HSCT is stable engraftment of donorderived hematopoietic cells, allowing them to differentiate and function normally, while not causing destruction of host tissues by donor-derived immune cells, resulting in GVHD. The presence of minor histocompatibility antigen (miHA) disparities between allogeneic individuals may induce GVHD, even when donor and recipient are matched at all MHC loci. Immunosuppressive drugs given after HSCT, or T cell depletion of the graft, can decrease the incidence and severity of GVHD (3). However, in the absence of mature T cells, many months are required to re-create an intact T cell immune system (4), leaving the recipient at great risk for opportunistic infection while a new T cell system arises from HSCs and undergoes thymic education ( Figure 1). The ability to infuse donor T cells that protect against infection and provide an antineoplastic effect, while excluding those T cells responsible for damaging normal tissues (observed in Graft-versus-host disease (GVHD) represents a major cause of morbidity and mortality following conventional allogeneic hematopoietic stem cell transplantation (HSCT). A study in mice (see related article on pages 101-108) demonstrates that the selective administration of donor memory CD4 + T cells results in immune reconstitution without GVHD, a result that, if translatable to humans, has important clinical implications for HSCT.

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“…Although they were suspicious of his story and motives, members of the hospital administration, hospital attorneys, and the public health department had to consider the potential legal options available for enforcing the isolation of a patient posing a potential threat to the public health. 3 When we were finally able to interview the patient's wife separately, she confirmed that they had come from Taiwan but had arrived one month, not five days, previously. She also confirmed that her husband had lost his job nine months earlier because of a drug problem.…”

Section: Pseudo-sarsmentioning

confidence: 99%