Biomedical subjects

Christine Bourgeois

Publications and source records attributed to Christine Bourgeois.

8 recordsLinked to original sources

PubMed2005

A major role for memory CD4 T cells in the control of lymphopenia-induced proliferation of naive CD4 T cells.

In a state of lymphopenia, naive and memory CD4 T cells compete with each other for expansion at the expense of naive T cells. This competition prevents the proliferation as well as the phenotypic and functional conversion of naive T cells to "memory-like" T cells and may consequently prevent immune pathology frequently associated with lymphopenia-induced proliferation of naive cells. However, in T cell replete mice, memory T cells do not compete with naive T cells, indicating independent homeostatic control of naive and memory CD4 T cells in conditions that do not involve profound lymphopenia. Moreover, within the memory compartment, subsequent generation of new memory T cells precludes the survival of memory-like T cells. Thus, memory T cells have a major role in the control of lymphopenia-induced proliferation of naive cells because they inhibit both the generation of memory-like T cells and their persistence within the memory compartment.

Adoptive Transfer↗

PubMed2004

Homeostasis and T cell regulation.

Homeostatic regulation of cell numbers is an important principle in biology. Mechanisms that function to maintain or re-establish homeostasis in the immune system include interactions among antigen-presenting cells, regulatory T cells and cytokines. The vital role that homeostatic regulation plays in maintaining a functionally intact immune system is illustrated by the perturbation of the peripheral T cell repertoire that occurs after lymphopenic incidents, which frequently provoke either exacerbated immune or autoimmune responses. Recent studies show that transient states of lymphopenia occur in viral infections and in the neonatal state and might be involved in the development of autoimmune diseases. On the positive side, lymphopenia-provoked T cell expansion might enhance weak immune responses and thereby aid the rejection of tumours or the elimination of parasites.

Animals↗

PubMed2004

CD4 T-cell memory.

CD4 T-cell memory is in some ways more enigmatic than CD8 T-cell memory. This is mostly due to the fact that CD4 T cells tend to expand far less in response to antigenic stimuli, thereby thwarting attempts at their detection during the course of an immune response. Nevertheless, there is a wide range of experimental models that have provided information regarding the survival and maintenance of CD4 memory cells, their functional capacities, their differentiation states and program of development following activation. The emerging picture is one of great versatility and functional heterogeneity as befits their central position within the immune system.

Animals↗

PubMed2003

On the role of MHC class II molecules in the survival and lymphopenia-induced proliferation of peripheral CD4+ T cells.

CD4(+) T cells expand after transfer into lymphopenic H-2(b) A(beta)-/- mice (I-A(beta)-, I-E(alpha)-deficient mice) but not after transfer into lymphopenic MHC II(Delta/Delta) mice (I-A(alpha)-, I-A(beta)-, I-E(alpha)-, and I-E(beta)-deficient mice), implying that in H-2(b) A(beta)-/- mice, A(alpha) chain and E(beta) chain associate to form a hybrid A(alpha)E(beta) MHC class II molecule. In light of this unexpected result, we reexamined the MHC class II requirement in the survival and lymphopenia-induced proliferation of CD4(+) T cells. Here we show that expansion, but not short-term survival, of CD4(+) T cells depends on interactions with MHC class II molecules in lymphopenic mice. Nevertheless, interactions with classical MHC class II molecules are required for CD4(+) T cells to survive in CD8(+) T-cell-containing mice.

Adoptive Transfer↗

PubMed2003

Mini-review CD4 T cells are required for CD8 T cell memory generation.

Whereas the role of CD4 T cells in B cell memory generation is well established and unequivocal, the role that CD4 T cells play in CD8 responses was until recently far more elusive and controversial. A series of recent reports, however, have re-assessed the role of CD4 help on CD8 responses and have given rise to surprisingly unambiguous conclusions. While studying very different systems, they demonstrated that CD4 T cells are absolutely required for the generation of bona fide CD8 memory cells; the reports allow, for the first time, strong analogies to be made between B and CD8 memory cell generation. These data invite us to drastically change our idea of CD4 help on CD8 responses because they show that the old dichotomy - Th-dependent versus Th-independent CD8 responses - is no longer accurate.

Animals↗

PubMed2002

A role for CD40 expression on CD8+ T cells in the generation of CD8+ T cell memory.

The delivery of CD4 help to CD8+ T cell responses requires interactions between CD40 and CD40 ligand and is thought to occur through antigen-presenting cell (APC) activation. Here we show that generation of memory CD8+ T cells displaying an enhanced capacity for cell division and cytokine secretion required CD4 help but not CD40 expression by the APCs. Activated CD4+ and CD8+ T cells expressed CD40; and in the absence of this protein, CD8+ T cells were unable to differentiate into memory cells or receive CD4 help. These results suggest that, like B cells, CD8+ T cells receive CD4 help directly through CD40 and that this interaction is fundamental for CD8+ T cell memory generation.

Animals↗

PubMed2002

Naive T cells proliferate strongly in neonatal mice in response to self-peptide/self-MHC complexes.

Adult naive T cells, which are at rest in normal conditions, proliferate strongly when transferred to lymphopenic hosts. In neonates, the first mature thymocytes to migrate to the periphery reach a compartment devoid of preexisting T cells. We have extensively analyzed the proliferation rate and phenotype of peripheral T cells from normal C57BL/6 and T cell antigen receptor transgenic mice as a function of age. We show that, like adult naive T cells transferred to lymphopenic mice, neonatal naive T cells proliferate strongly. By using bone-marrow transfer and thymic-graft models, we demonstrate that the proliferation of the first thymic emigrants reaching the periphery requires T cell antigen receptor-self-peptide/self-MHC interactions and is regulated by the size of the peripheral T cell pool.

Animals↗

PubMed2002

CD8 lethargy in the absence of CD4 help.

CD4 T cell help was proposed to have a pivotal role in orienting CD8 T cell responses to antigen stimulation. By activating antigen-presenting cells (APC), CD4 cells would induce their expression of costimulatory molecules, the "signal two" required to induce full CD8 activation, preventing CD8 tolerance. Recent data on this subject is contradictory, as the absence of help did not always result in CD8 tolerance. These differences were attributed either to the presence of residual CD4 help or, respectively to the type of antigen stimulation, the peptide affinity, the CTL frequencies, and/or the strength of the response. We therefore reassessed the role of CD4 help in CD8 responses using a system where CD4 cells are absent and APC not activated. This system can be manipulated to induce CD8 tolerance (at high antigen concentrations) or CD8 memory (at low antigen concentrations). We found that the presence of CD4 help did not prevent tolerance induction. On the other hand, the absence of CD4 help did not induce CD8 tolerance, but rather led to differentiation stage intermediate between naive/memory/tolerant cells that we call "lethargy". These findings indicate that role of CD4 help in CD8 responses does not follow a simple on-off rule, as previously suggested. They also reveal that the "tolerance versus memory" dichotomy fails to account for all possible states/properties of antigen-experienced CD8 cells. Depending on the priming conditions, other intermediate stages of differentiation may occur.

Animals↗