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Are major histocompatibility complex molecules involved in the survival of naive CD4+ T cells?

Grandjean I, Duban L, Bonney EA, Corcuff E, Di Santo JP, Matzinger P, Lantz O - J. Exp. Med. (2003)

Bottom Line: We found that naive T cells transferred into MHC negative or allogeneic environments often fail to survive because of rejection and/or competition by natural killer (NK) cells, rather than failure to recognize a particular MHC allele.Therefore, space-induced expansion and survival are two different phenomena displaying different MHC requirements.Memory CD4+ T cells, whose survival and expansion showed no requirements for MHC molecules at all, dampened the space-induced expansion of naive cells, showing that the two populations are not independent in their requirements for peripheral niches.

View Article: PubMed Central - PubMed

Affiliation: Laboratoire d'Immunologie, Institut Curie, 26 rue d'Ulm, 75005 Paris, France.

ABSTRACT
The exact role of major histocompatibility complex (MHC) molecules in the peripheral survival of naive T cells is controversial, as some studies have suggested that they are critically required whereas others have suggested that they are not. Here we controlled for some of the features that differed among the earlier studies, and analyzed both the survival and expansion of naive CD4+ T cells transferred into MHC syngeneic, allogeneic, or MHC negative environments. We found that naive T cells transferred into MHC negative or allogeneic environments often fail to survive because of rejection and/or competition by natural killer (NK) cells, rather than failure to recognize a particular MHC allele. In the absence of NK cells, naive CD4+ T cells survived equally well regardless of the MHC type of the host. There was, however, an MHC requirement for extensive space-induced "homeostatic" expansion. Although the first few divisions occurred in the absence of MHC molecules, the cells did not continue to divide or transit to a CD44hi phenotype. Surprisingly, this MHC requirement could be satisfied by alleles other than the restricting haplotype. Therefore, space-induced expansion and survival are two different phenomena displaying different MHC requirements. Memory CD4+ T cells, whose survival and expansion showed no requirements for MHC molecules at all, dampened the space-induced expansion of naive cells, showing that the two populations are not independent in their requirements for peripheral niches.

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Survival, expansion, and transition to the CD44hi state of naive T cells in different hosts. 105 CFSE-labeled mature CD4+ thymocytes (B) or lymph node CD4+ T cells (A and C) were injected into either empty hosts (A and B), or hosts prefilled with memory cells (C), of the indicated MHC types. The left-most panel represents the total number of cells recovered and the three right-hand panels show the number of cells in the different subsets as defined in Fig. 4 B. The data represent individual recipients in nine independent experiments (four, two, and three experiments each in A, B, and C, respectively). Due to loss of samples there are only two experiments represented for subsets 2 and 3 in C. At days 21 and 42, the data for H-2b recipients in B are represented as small crosses. These numbers are imprecise because the recovered cell populations contain some cells generated by development in the host thymus. Being CFSE−, these cells are impossible to distinguish from any transferred cells that have undergone many divisions.
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fig5: Survival, expansion, and transition to the CD44hi state of naive T cells in different hosts. 105 CFSE-labeled mature CD4+ thymocytes (B) or lymph node CD4+ T cells (A and C) were injected into either empty hosts (A and B), or hosts prefilled with memory cells (C), of the indicated MHC types. The left-most panel represents the total number of cells recovered and the three right-hand panels show the number of cells in the different subsets as defined in Fig. 4 B. The data represent individual recipients in nine independent experiments (four, two, and three experiments each in A, B, and C, respectively). Due to loss of samples there are only two experiments represented for subsets 2 and 3 in C. At days 21 and 42, the data for H-2b recipients in B are represented as small crosses. These numbers are imprecise because the recovered cell populations contain some cells generated by development in the host thymus. Being CFSE−, these cells are impossible to distinguish from any transferred cells that have undergone many divisions.

Mentions: Naive cells behaved differently from memory cells (Fig. 4 B) and could be classed into three stages on the basis of cell division and CD44 expression. Some cells did not divide at all for up to 6 wk (stage 1), other cells divided somewhat (though more slowly than the memory T cells), but did not transit to the CD44hi state (stage 2), and in MHC+ hosts, others continued to divide such that they lost enough of the CFSE dye to appear negative, and up-regulated CD44 (stage 3). Because of their extensive proliferation, cells in this latter group comprised 70–81% of the recovered cells and were therefore the main arbiters of any differences seen in total cell recovery. An analysis of these three stages in nine separate experiments (Fig. 5) showed that the number of cells in each stage varied according to the MHC context, the presence or the absence of memory T cells, and the maturational state of the naive CD4+ cells (lymph node vs. thymus origin).


Are major histocompatibility complex molecules involved in the survival of naive CD4+ T cells?

Grandjean I, Duban L, Bonney EA, Corcuff E, Di Santo JP, Matzinger P, Lantz O - J. Exp. Med. (2003)

Survival, expansion, and transition to the CD44hi state of naive T cells in different hosts. 105 CFSE-labeled mature CD4+ thymocytes (B) or lymph node CD4+ T cells (A and C) were injected into either empty hosts (A and B), or hosts prefilled with memory cells (C), of the indicated MHC types. The left-most panel represents the total number of cells recovered and the three right-hand panels show the number of cells in the different subsets as defined in Fig. 4 B. The data represent individual recipients in nine independent experiments (four, two, and three experiments each in A, B, and C, respectively). Due to loss of samples there are only two experiments represented for subsets 2 and 3 in C. At days 21 and 42, the data for H-2b recipients in B are represented as small crosses. These numbers are imprecise because the recovered cell populations contain some cells generated by development in the host thymus. Being CFSE−, these cells are impossible to distinguish from any transferred cells that have undergone many divisions.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2194222&req=5

fig5: Survival, expansion, and transition to the CD44hi state of naive T cells in different hosts. 105 CFSE-labeled mature CD4+ thymocytes (B) or lymph node CD4+ T cells (A and C) were injected into either empty hosts (A and B), or hosts prefilled with memory cells (C), of the indicated MHC types. The left-most panel represents the total number of cells recovered and the three right-hand panels show the number of cells in the different subsets as defined in Fig. 4 B. The data represent individual recipients in nine independent experiments (four, two, and three experiments each in A, B, and C, respectively). Due to loss of samples there are only two experiments represented for subsets 2 and 3 in C. At days 21 and 42, the data for H-2b recipients in B are represented as small crosses. These numbers are imprecise because the recovered cell populations contain some cells generated by development in the host thymus. Being CFSE−, these cells are impossible to distinguish from any transferred cells that have undergone many divisions.
Mentions: Naive cells behaved differently from memory cells (Fig. 4 B) and could be classed into three stages on the basis of cell division and CD44 expression. Some cells did not divide at all for up to 6 wk (stage 1), other cells divided somewhat (though more slowly than the memory T cells), but did not transit to the CD44hi state (stage 2), and in MHC+ hosts, others continued to divide such that they lost enough of the CFSE dye to appear negative, and up-regulated CD44 (stage 3). Because of their extensive proliferation, cells in this latter group comprised 70–81% of the recovered cells and were therefore the main arbiters of any differences seen in total cell recovery. An analysis of these three stages in nine separate experiments (Fig. 5) showed that the number of cells in each stage varied according to the MHC context, the presence or the absence of memory T cells, and the maturational state of the naive CD4+ cells (lymph node vs. thymus origin).

Bottom Line: We found that naive T cells transferred into MHC negative or allogeneic environments often fail to survive because of rejection and/or competition by natural killer (NK) cells, rather than failure to recognize a particular MHC allele.Therefore, space-induced expansion and survival are two different phenomena displaying different MHC requirements.Memory CD4+ T cells, whose survival and expansion showed no requirements for MHC molecules at all, dampened the space-induced expansion of naive cells, showing that the two populations are not independent in their requirements for peripheral niches.

View Article: PubMed Central - PubMed

Affiliation: Laboratoire d'Immunologie, Institut Curie, 26 rue d'Ulm, 75005 Paris, France.

ABSTRACT
The exact role of major histocompatibility complex (MHC) molecules in the peripheral survival of naive T cells is controversial, as some studies have suggested that they are critically required whereas others have suggested that they are not. Here we controlled for some of the features that differed among the earlier studies, and analyzed both the survival and expansion of naive CD4+ T cells transferred into MHC syngeneic, allogeneic, or MHC negative environments. We found that naive T cells transferred into MHC negative or allogeneic environments often fail to survive because of rejection and/or competition by natural killer (NK) cells, rather than failure to recognize a particular MHC allele. In the absence of NK cells, naive CD4+ T cells survived equally well regardless of the MHC type of the host. There was, however, an MHC requirement for extensive space-induced "homeostatic" expansion. Although the first few divisions occurred in the absence of MHC molecules, the cells did not continue to divide or transit to a CD44hi phenotype. Surprisingly, this MHC requirement could be satisfied by alleles other than the restricting haplotype. Therefore, space-induced expansion and survival are two different phenomena displaying different MHC requirements. Memory CD4+ T cells, whose survival and expansion showed no requirements for MHC molecules at all, dampened the space-induced expansion of naive cells, showing that the two populations are not independent in their requirements for peripheral niches.

Show MeSH
Related in: MedlinePlus