CD4 T Cell-Dependent Conditioning of Dendritic Cells to Produce IL-12 Results in CD8-Mediated Graft Rejection and Avoidance of Tolerance

Filatenkov, Alexander; Jacovetty, Erica L.; Fischer, Ursula B.; Curtsinger, Julie; Mescher, Matthew F.; Ingulli, Elizabeth

doi:10.4049/jimmunol.174.11.6909

Cited by 73 publications

(80 citation statements)

References 43 publications

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“…[33] examining an ectopic heart transplant model. In this model, donor mice expressed a membrane form of ovalbumin (mOVA) as a transgene under the control of an actin promoter, so that OVA was expressed in all tissues, including the heart.…”

Section: Cd4 T Helper Cells Condition DC To Provide Signalmentioning

confidence: 99%

Molecular basis for checkpoints in the CD8 T cell response: Tolerance versus activation

Mescher¹,

Agarwal²,

Casey³

et al. 2007

Seminars in Immunology

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CD8 T cells specific for self-antigens are present in the peripheral lymphoid system and can contribute to autoimmunity or transplant rejection. Whether recognition of Ag leads to full activation, or to induction of tolerance, depends upon availability of cytokine at critical stages of the response. Signals provided by IL-12 and/or IFN-α/β are required for activation of naïve CD8 T cells, and IL-2 is needed to sustain and further expand the effector cells if Ag persists. These critical signaling requirements provide new insights into the factors that regulate the CD8 T cell contributions to development of autoimmunity or rejection of transplants.

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Section: Cd4 T Helper Cells Condition DC To Provide Signalmentioning

confidence: 99%

Molecular basis for checkpoints in the CD8 T cell response: Tolerance versus activation

Mescher¹,

Agarwal²,

Casey³

et al. 2007

Seminars in Immunology

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“…Trafficking of IC Ag following brain injury is highly immunogenic; nevertheless, cross-priming is dependent on CD4 ϩ T cell help. Based on the failure to cross-prime T cells in CD40 Ϫ/Ϫ mice, we believe this helper response acts via a "licensing" event that is similar to what has been shown for other cell-restricted Ags (18,24). This experimental system will permit the further characterization of effector mechanisms relevant to the pathogenesis of CNS immune disorders.…”

Section: Resultsmentioning

confidence: 98%

Cutting Edge: Cross-Presented Intracranial Antigen Primes CD8+ T Cells

Walter

Albert

2007

The Journal of Immunology

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The CNS is considered immune privileged due to the blood-brain barrier and the absence of conventional lymphatics. Nonetheless, T cell immune responses specific for CNS Ag have been documented. Where these events are initiated and what cellular mechanisms are involved remain unknown. In this study, we established an experimental mouse model to evaluate the requirements for priming CD8+ T cells following the cross-presentation of intracranial Ag. Surprisingly, we find that even with a damaged blood-brain barrier, Ag presentation occurs in regional lymph nodes and not within the CNS itself. Only once the responding cells have expanded can they traffic to the site of CNS injury. Cross-presentation of intracranial Ag is efficient and the subsequent priming of CD8+ T cells is dependent on CD4+ T cell help and CD40 signaling in host APCs. Our findings have important implications for the initiation of T cell immune responses toward CNS Ags.

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“…Also, the finding of an alloreactive T cell response against the allele HLA-A*0101 in the mother of this family does not allow us to determine whether the detectable levels of this response resulted from "natural alloreactivity" or if it was the result of previous sensitization from multiple exposures against HLA-A*0101 through pregnancy; some cytotoxic T cells may recognize HLA molecules encoded by other alleles by direct recognition, loaded with antigenic peptides including the amino acid Arg 48 peptide derived from the H chain of HLA-A*0101 in the absence of lymphocyte priming such as that provided by the MLC. But cytokines such as IL-12 and IFN-␥ are produced by Th cells to influence CD8 ϩ T cell activity (23). The weak response against the mismatch in HLA-A*01, in the absence of incompatibility in HLA class II alleles between stimulator and responder individuals, could result in stimulation by minor histocompatibility Ags that may have induced weak T cell responses (24,25).…”

Section: Discussionmentioning

confidence: 99%

Allorecognition of an HLA-A01 Aberrant Allele by an HLA Identical Family Member Carrying the HLA-A0101 Allele

Almeciga

Wang

Zúñiga

et al. 2006

The Journal of Immunology

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We identified and characterized an HLA-A1 aberrant allele (A*0118N) resulting from a novel molecular mechanism; this allele was present in an unusually informative family with a near identical parental HLA haplotype (c d) differing only by one nucleotide substitution in one HLA-A allele, A*0118N, of the maternal HLA haplotype (c) and not of the paternal HLA haplotype (a). Although serologic HLA typing showed a “blank,” DNA molecular HLA typing detected a HLA-A*0118N allele. Sequence based typing identified the substitution of guanine by cytosine at the nucleotide position 215, which resulted in the replacement of arginine by proline at position 48 of the HLA-A1 H chain. The loss of surface protein expression was also found by FACS analysis. Isoelectric-focusing analysis detected a HLA-A H chain with a unique isoelectric-focusing pattern, which does not associate with the L chain (β2-microglobulin). These results suggest that the residue 48-containing interaction site on the α1 domain plays a critical role in the association between HLA class I H chain and β2-microglobulin. Functional studies showed that the T cells of the propositus (HLA haplotypes c d) carrying this null allele recognized its wild-type counterpart, HLA-A*010101, in her HLA-identical son that carries the HLA-A*0101 heterodimer. This is the first example of the generation of cytotoxic T cells in the absence of proliferation of CD4+ T cells (mixed lymphocyte culture) and the description of an aberrant allele, A*0118N, that may behave as a minor histocompatibility Ag, with implications in allorecognition by cytolytic T cells in solid organ and stem cell transplantation.

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CD4 T Cell-Dependent Conditioning of Dendritic Cells to Produce IL-12 Results in CD8-Mediated Graft Rejection and Avoidance of Tolerance

Cited by 73 publications

References 43 publications

Molecular basis for checkpoints in the CD8 T cell response: Tolerance versus activation

Molecular basis for checkpoints in the CD8 T cell response: Tolerance versus activation

Cutting Edge: Cross-Presented Intracranial Antigen Primes CD8+ T Cells

Allorecognition of an HLA-A01 Aberrant Allele by an HLA Identical Family Member Carrying the HLA-A0101 Allele

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CD4 T Cell-Dependent Conditioning of Dendritic Cells to Produce IL-12 Results in CD8-Mediated Graft Rejection and Avoidance of Tolerance

Cited by 73 publications

References 43 publications

Molecular basis for checkpoints in the CD8 T cell response: Tolerance versus activation

Molecular basis for checkpoints in the CD8 T cell response: Tolerance versus activation

Cutting Edge: Cross-Presented Intracranial Antigen Primes CD8+ T Cells

Allorecognition of an HLA-A*01 Aberrant Allele by an HLA Identical Family Member Carrying the HLA-A*0101 Allele

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Product

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About

Allorecognition of an HLA-A01 Aberrant Allele by an HLA Identical Family Member Carrying the HLA-A0101 Allele