Degeneracy of H‐2 recognition by cytotoxic T lymphocytes: 10% of the total repertoire is “specific” for a given haplotype and up to 1% is self‐H‐2 reactive

Beretta, Alberto; Ermonval, Myriam; Larsson, Eva‐Lotta

doi:10.1002/eji.1830160604

Cited by 9 publications

(2 citation statements)

References 26 publications

(8 reference statements)

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“…About half of the grafted scid(Ig') mice completely rejected their H-2 k allografts (see Table IV). This suggests that many scid(Ig') mice may contain -20-40 functional T cell precursors, assuming that 1 in every 20 precursors can recognize a given foreign MHC haplotype (42,43) and that the progeny of 1-2 precursors is sufficient to mediate allograft rejection . Nonetheless, the T cell repertoire must be very restricted since half of the grafted scid(Ig') mice failed to reject (or completely reject) their allografts.…”

Section: Elapsed Timementioning

confidence: 99%

Evidence of functional lymphocytes in some (leaky) scid mice.

Bosma

Fried

Custer

et al. 1988

The Journal of Experimental Medicine

303

141

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Lymphoid and myeloid cells represent distinct lineages of a common hematopoietic stem cell (1-3). This distinction is dramatically illustrated in the autosomal recessive mouse mutant, scid . t Mice homozygous for the scid mutation (scid mice) are severely deficient in B and T lymphocytes whereas other hematopoietic cell types such as erythrocytes, monocytes, granulocytes, and megakaryocytes (all members of the myeloid series) are present in normal number (4, 5). Although the scid mutation appears to affect only lymphocyte development (4-10), it is not yet clear what stage of lymphoid differentiation is impaired or arrested .Recent results suggest that the effects of the scid mutation become manifest after the commitment of lymphoid cells to the B and T cell pathways . First, early transcription of unrearranged H chain and TCR loci, which presumably signals the opening of these loci to factors responsible for gene recombination (11-16), is detectable in scid fetal liver and thymus, respectively (Schuler, W., A. Schuler, and M. J. Bosma, unpublished results) . Second, although cells with H chain (or TCR) gene rearrangements cannot be directly demonstrated in freshly harvested lymphoid tissues of adult scid mice (17), early B cell lines with H chain gene rearrangements can be recovered from Abelson murine leukemia virus-transformed scid bone marrow cells (17) and from long-term cultures of scid bone marrow cells (18). There is also indication of early T cell development as thymic lymphomas with rearranged TCR-'Y and TCR-# alleles spontaneously appear in -15% of scid mice (5,17,19). It is striking, however, that the majority of rearranged H chain and TCR alleles in transformed scid lymphocytes show abnormal J region deletions. The deletions remove all J-coding exons of a given J region and appear to result from attempted D to J or V to Jjoining; they vary in size and extend both 5' and 3' of the deleted J regions (17,19). Evidence of abnormal J-associated deletions has also been reported for rearranged H chain alleles of long-term B cell lines derived from scid bone marrow cells (18).To explain the abnormal J-associated deletions and how they might account

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Section: Elapsed Timementioning

confidence: 99%

Evidence of functional lymphocytes in some (leaky) scid mice.

Bosma

Fried

Custer

et al. 1988

The Journal of Experimental Medicine

303

141

View full text Add to dashboard Cite

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“…Although autologous mixed lymphocyte reaction provides prima facie evidence for the existence of autoreactive T lymphocytes in man [5] and the precursor frequency of autocytotoxic T cells has been estimated both in man [17] and in mice [18], this concept has been recently challenged by the possibility that such a reaction is an in vitro artefact due to the contamina tion of the culture system by exogenous antigens such as red blood cells (used for rosetting) or serum pro teins [19]. The experimental system used excludes that such contaminations are responsible for autoreactive T cell activation: in fact, we used nylon wool filtration to enrich the responder population, and the medium used for cultures was supplemented with human serum and the developed clones proliferate also in serum-free medium.…”

Section: Discussionmentioning

confidence: 99%

Increased Autoreactive T Cell Frequency in Tuberculous Patients

Gallo¹,

Lombardi²,

Piccolella³

et al. 1990

Int Arch Allergy Immunol

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The development of putative self-MHC-reactive T cells and their precursor frequency was estimated in peripheral blood lymphocyte cultures stimulated in vitro with PPD. The role of foreign antigen in the generation of self-MHC-reactive T cells in vivo was analyzed by comparing the frequency of autoreactive T cells in the peripheral blood of tuberculous patients with that observed in healthy individuals. It was found that PPD in vitro and Mycobacterium tuberculosis infection in vivo increased substantially the generation of autoreactive T cells. Autoreactive T cell clones were shown (1) to recognize self MHC class II products; (2) to release gamma interferon in the absence of exogenous antigen, and (3) to express autocytotoxic activity. All these findings suggest that self-MHC-reactive T cells may be involved in the inflammatory response to M. tuberculosis.

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